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ALLERGOLOGY AND IMMUNOLOGY (212 journals)                  1 2 | Last

Showing 1 - 200 of 212 Journals sorted alphabetically
Acta Microbiologica et Immunologica Hungarica     Full-text available via subscription   (Followers: 4)
Advances in Immunology     Full-text available via subscription   (Followers: 37)
AIDS Research and Therapy     Open Access   (Followers: 14)
Alergologia Polska : Polish Journal of Allergology     Full-text available via subscription   (Followers: 1)
Allergies     Open Access   (Followers: 1)
Allergo Journal     Full-text available via subscription   (Followers: 1)
Allergo Journal International     Hybrid Journal   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1)
Allergology International     Open Access   (Followers: 5)
Allergy     Hybrid Journal   (Followers: 50)
Allergy & Rhinology     Open Access   (Followers: 4)
Allergy and Asthma Proceedings     Full-text available via subscription   (Followers: 14)
Allergy, Asthma and Clinical Immunology     Open Access   (Followers: 26)
American Journal of Epidemiology     Hybrid Journal   (Followers: 216)
American Journal of Immunology     Open Access   (Followers: 23)
American Journal of Preventive Medicine     Hybrid Journal   (Followers: 29)
American Journal of Reproductive Immunology     Hybrid Journal   (Followers: 6)
American Journal of Rhinology and Allergy     Hybrid Journal   (Followers: 9)
Annals of Allergy, Asthma and Immunology     Hybrid Journal   (Followers: 14)
Annals of Allergy, Asthma, and Immunology     Hybrid Journal  
Annual Review of Immunology     Full-text available via subscription   (Followers: 50)
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry     Hybrid Journal   (Followers: 5)
Applied Immunohistochemistry & Molecular Morphology     Hybrid Journal   (Followers: 16)
Archives of Asthma, Allergy and Immunology     Open Access  
Archivum Immunologiae et Therapiae Experimentalis     Hybrid Journal   (Followers: 2)
Autoimmune Diseases     Open Access   (Followers: 3)
Autoimmunity     Hybrid Journal   (Followers: 9)
Autoimmunity Highlights     Open Access   (Followers: 2)
Autoimmunity Reviews     Hybrid Journal   (Followers: 3)
BMC Immunology     Open Access   (Followers: 11)
Cancer Immunology, Immunotherapy     Hybrid Journal   (Followers: 22)
Case Reports in Immunology     Open Access   (Followers: 6)
Cellular & Molecular Immunology     Hybrid Journal   (Followers: 15)
Cellular Immunology     Hybrid Journal   (Followers: 31)
Chronic Diseases and Injuries in Canada     Free   (Followers: 1)
Clinica Chimica Acta     Hybrid Journal   (Followers: 28)
Clinical & Experimental Allergy     Hybrid Journal   (Followers: 7)
Clinical & Experimental Allergy Reviews     Hybrid Journal   (Followers: 1)
Clinical & Experimental Immunology     Hybrid Journal   (Followers: 18)
Clinical & Translational Immunology     Open Access   (Followers: 8)
Clinical and Experimental Neuroimmunology     Hybrid Journal   (Followers: 1)
Clinical and Molecular Allergy     Open Access   (Followers: 5)
Clinical and Translational Allergy     Open Access   (Followers: 2)
Clinical Immunology     Hybrid Journal   (Followers: 25)
Clinical Immunology, Endocrine & Metabolic Drugs     Hybrid Journal  
Clinical Reviews in Allergy and Immunology     Hybrid Journal   (Followers: 12)
Comparative Immunology, Microbiology and Infectious Diseases     Hybrid Journal   (Followers: 14)
Critical Reviews in Immunology     Full-text available via subscription   (Followers: 15)
Current Allergy & Clinical Immunology     Open Access   (Followers: 8)
Current Allergy and Asthma Reports     Hybrid Journal   (Followers: 2)
Current Immunology Reviews     Hybrid Journal   (Followers: 10)
Current Opinion in Allergy and Clinical Immunology     Hybrid Journal   (Followers: 8)
Current Opinion in Immunology     Hybrid Journal   (Followers: 44)
Current Opinion in Virology     Hybrid Journal   (Followers: 1)
Current Protocols in Immunology     Hybrid Journal  
Current Treatment Options in Allergy     Hybrid Journal   (Followers: 2)
Developmental & Comparative Immunology     Hybrid Journal   (Followers: 7)
Egyptian Journal of Pediatric Allergy and Immunology     Open Access   (Followers: 2)
Emerging Infectious Diseases     Open Access   (Followers: 30)
Epidemiologic Methods     Hybrid Journal   (Followers: 4)
European Annals of Allergy and Clinical Immunology     Open Access   (Followers: 5)
European Journal of Immunology     Hybrid Journal   (Followers: 39)
European Journal of Microbiology and Immunology     Open Access   (Followers: 11)
Expert Review of Clinical Immunology     Full-text available via subscription   (Followers: 5)
Expert Review of Vaccines     Full-text available via subscription   (Followers: 4)
Food and Agricultural Immunology     Open Access   (Followers: 2)
Frontiers in Immunology     Open Access   (Followers: 20)
Future Virology     Hybrid Journal   (Followers: 8)
Genes & Immunity     Hybrid Journal   (Followers: 8)
Handbook of Systemic Autoimmune Diseases     Full-text available via subscription   (Followers: 2)
HLA Immune Response Genetics     Hybrid Journal  
HNO Nachrichten     Full-text available via subscription  
Human Immunology     Hybrid Journal   (Followers: 18)
Human Vaccines & Immunotherapeutics     Full-text available via subscription   (Followers: 2)
Hypersensitivity     Open Access   (Followers: 1)
Immunity     Full-text available via subscription   (Followers: 65)
Immunity & Ageing     Open Access   (Followers: 10)
Immunity, Inflammation and Disease     Open Access   (Followers: 6)
Immuno-analyse & Biologie Spécialisée     Full-text available via subscription   (Followers: 2)
Immunobiology     Hybrid Journal   (Followers: 9)
Immunoendocrinology     Open Access   (Followers: 1)
Immunogenetics     Hybrid Journal   (Followers: 6)
ImmunoHorizons     Open Access  
Immunologic Research     Hybrid Journal   (Followers: 6)
Immunological Investigations: A Journal of Molecular and Cellular Immunology     Hybrid Journal   (Followers: 2)
Immunological Medicine     Open Access  
Immunological Reviews     Hybrid Journal   (Followers: 27)
Immunology     Hybrid Journal   (Followers: 38)
Immunology & Cell Biology     Hybrid Journal   (Followers: 9)
Immunology and Allergy Clinics of North America     Full-text available via subscription   (Followers: 6)
Immunology and Immunogenetic Insights     Open Access   (Followers: 5)
Immunology and Infectious Diseases     Open Access   (Followers: 9)
Immunology Innovation     Open Access   (Followers: 2)
Immunology Letters     Hybrid Journal   (Followers: 13)
Immunology, Endocrine & Metabolic Agents - Medicinal Chemistry     Hybrid Journal   (Followers: 3)
Immunome Research     Open Access   (Followers: 6)
ImmunoTargets and Therapy     Open Access   (Followers: 2)
Immunotherapy     Hybrid Journal   (Followers: 7)
Immunotoxicology of Drugs and Chemicals: an Experimental and Clinical Approach     Full-text available via subscription   (Followers: 1)
Indian Journal of Allergy, Asthma and Immunology     Open Access   (Followers: 1)
Infectious Diseases: Research and Treatment     Open Access   (Followers: 4)
Inflammation & Allergy - Drug Targets     Hybrid Journal   (Followers: 2)
Inmunología     Full-text available via subscription   (Followers: 2)
Innate Immunity     Hybrid Journal   (Followers: 7)
International Archives of Allergy and Immunology     Full-text available via subscription   (Followers: 1)
International Forum of Allergy & Rhinology     Hybrid Journal   (Followers: 4)
International Immunology     Hybrid Journal   (Followers: 3)
International Immunopharmacology     Hybrid Journal   (Followers: 2)
International Journal of Immunological Studies     Hybrid Journal   (Followers: 1)
International Journal of Immunopathology and Pharmacology     Full-text available via subscription   (Followers: 2)
International Journal of Infectious Diseases     Open Access   (Followers: 9)
International Journal of Virology     Open Access   (Followers: 2)
International Reviews Of Immunology     Hybrid Journal   (Followers: 4)
Internet Journal of Rheumatology and Clinical Immunology     Open Access   (Followers: 5)
Iranian Journal of Allergy, Asthma and Immunology     Open Access  
Joint Commission Journal on Quality and Patient Safety     Hybrid Journal   (Followers: 40)
Journal des Anti-infectieux     Full-text available via subscription   (Followers: 2)
Journal of Allergy & Therapy     Open Access   (Followers: 2)
Journal of Clinical & Cellular Immunology     Open Access   (Followers: 3)
Journal of Vaccines & Vaccination     Open Access   (Followers: 4)
Journal of Allergy and Clinical Immunology     Hybrid Journal   (Followers: 31)
Journal of Allergy and Clinical Immunology : In Practice     Full-text available via subscription   (Followers: 13)
Journal of Asthma Allergy Educators     Hybrid Journal   (Followers: 4)
Journal of Asthma and Allergy     Open Access   (Followers: 8)
Journal of Autoimmunity     Hybrid Journal   (Followers: 15)
Journal of Cellular Immunotherapy     Open Access   (Followers: 4)
Journal of Clinical Immunology     Hybrid Journal   (Followers: 14)
Journal of Clinical Immunology and Immunopathology Research     Open Access   (Followers: 5)
Journal of General Virology     Full-text available via subscription   (Followers: 11)
Journal of Immune Based Therapies, Vaccines and Antimicrobials     Open Access   (Followers: 2)
Journal of Immunological Methods     Hybrid Journal   (Followers: 46)
Journal of Immunological Techniques in Infectious Diseases     Hybrid Journal   (Followers: 3)
Journal of Immunology     Full-text available via subscription   (Followers: 68)
Journal of Immunology and Clinical Microbiology     Open Access   (Followers: 2)
Journal of Immunology and Regenerative Medicine     Hybrid Journal   (Followers: 1)
Journal of Immunology Research     Open Access   (Followers: 9)
Journal of Immunotherapy     Hybrid Journal   (Followers: 7)
Journal of Immunotherapy Applications     Open Access  
Journal of Immunotoxicology     Open Access   (Followers: 3)
Journal of Infection Prevention     Hybrid Journal   (Followers: 16)
Journal of Infectious Diseases and Immunity     Open Access   (Followers: 8)
Journal of Innate Immunity     Open Access   (Followers: 6)
Journal of Medical Genetics and Genomics     Open Access   (Followers: 3)
Journal of Microbiology, Immunology and Infection     Open Access   (Followers: 9)
Journal of Neuroimmunology     Hybrid Journal   (Followers: 6)
Journal of NeuroVirology     Hybrid Journal   (Followers: 1)
Journal of Reproductive Immunology     Hybrid Journal   (Followers: 2)
Journal of the Pediatric Infectious Diseases Society     Hybrid Journal   (Followers: 11)
Journal of Translational Autoimmunity     Open Access  
Medical Immunology     Open Access   (Followers: 20)
Medical Microbiology and Immunology     Hybrid Journal   (Followers: 7)
Microbiology and Immunology     Hybrid Journal   (Followers: 10)
Molecular Immunology     Hybrid Journal   (Followers: 17)
Mucosal Immunology     Hybrid Journal   (Followers: 6)
Nature Immunology     Full-text available via subscription   (Followers: 309)
Nature Reviews Immunology     Full-text available via subscription   (Followers: 293)
Neuroimmunology and Neuroinflammation     Open Access   (Followers: 3)
NeuroImmunoModulation     Full-text available via subscription   (Followers: 2)
Neurology : Neuroimmunology & Neuroinflammation     Open Access   (Followers: 4)
npj Vaccines     Hybrid Journal  
OA Immunology     Open Access  
Ocular Immunology & Inflammation     Hybrid Journal   (Followers: 9)
OncoImmunology     Full-text available via subscription   (Followers: 3)
Open Allergy Journal     Open Access  
Open Cancer Immunology Journal     Open Access  
Open Forum Infectious Diseases     Open Access   (Followers: 4)
Open Immunology Journal     Open Access  
Open Journal of Immunology     Open Access   (Followers: 5)
Open Virology Journal     Open Access  
Oral Microbiology and Immunology     Hybrid Journal   (Followers: 1)
Papillomavirus Research     Open Access  
Parasite Immunology     Hybrid Journal   (Followers: 3)
Pediatric Allergy and Immunology     Hybrid Journal   (Followers: 38)
Perspectives in Vaccinology     Open Access   (Followers: 1)
Photodermatology, Photoimmunology & Photomedicine     Hybrid Journal   (Followers: 3)
Polish Pneumonology and Allergology     Open Access   (Followers: 1)
Procedia in Vaccinology     Open Access   (Followers: 2)
Recent Patents on Inflammation & Allergy Drug Discovery     Hybrid Journal   (Followers: 2)
Research & Reviews : A Journal of Immunology     Full-text available via subscription   (Followers: 6)
Research Journal of Allergy     Open Access   (Followers: 3)
Research Journal of Immunology     Open Access   (Followers: 3)
Results in Immunology     Open Access   (Followers: 4)
Revista Alergia México     Open Access  
Revista Portuguesa de Imunoalergologia     Open Access   (Followers: 2)
Revue Française d'Allergologie     Full-text available via subscription   (Followers: 3)
Russian Journal of Infection and Immunity     Open Access   (Followers: 20)
Scandinavian Journal of Immunology     Hybrid Journal   (Followers: 10)
Science Immunology     Full-text available via subscription   (Followers: 16)
Self/Nonself - Immune Recognition and Signaling     Full-text available via subscription   (Followers: 2)
Seminars in Immunology     Hybrid Journal   (Followers: 13)
Seminars in Immunopathology     Hybrid Journal   (Followers: 3)
Sinusitis     Open Access  
South East European Journal of Immunology     Open Access  
Therapeutic Advances in Vaccines     Hybrid Journal   (Followers: 1)
Therapeutic Advances in Vaccines and Immunotherapy     Open Access  
Toxicology and Environmental Health Sciences     Hybrid Journal   (Followers: 6)
Transactions of the Royal Society of Tropical Medicine and Hygiene     Hybrid Journal   (Followers: 4)
Transplant Immunology     Hybrid Journal   (Followers: 8)
Transplantation     Hybrid Journal   (Followers: 20)
Trends in Immunology     Full-text available via subscription   (Followers: 54)

        1 2 | Last

Similar Journals
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Frontiers in Immunology
Journal Prestige (SJR): 2.803
Citation Impact (citeScore): 6
Number of Followers: 20  

  This is an Open Access Journal Open Access journal
ISSN (Online) 1664-3224
Published by Frontiers Media Homepage  [85 journals]
  • Complex Stability and an Irrevertible Transition Reverted by Peptide and
           Fibroblasts in a Dynamic Model of Innate Immunity

    • Authors: Abulikemu Abudukelimu, Matteo Barberis, Frank Redegeld, Nilgun Sahin, Raju P. Sharma, Hans V. Westerhoff
      Abstract: We here apply a control analysis and various types of stability analysis to an in silico model of innate immunity that addresses the management of inflammation by a therapeutic peptide. Motivation is the observation, both in silico and in experiments, that this therapy is not robust. Our modeling results demonstrate how (1) the biological phenomena of acute and chronic modes of inflammation may reflect an inherently complex bistability with an irrevertible flip between the two modes, (2) the chronic mode of the model has stable, sometimes unique, steady states, while its acute-mode steady states are stable but not unique, (3) as witnessed by TNF levels, acute inflammation is controlled by multiple processes, whereas its chronic-mode inflammation is only controlled by TNF synthesis and washout, (4) only when the antigen load is close to the acute mode's flipping point, many processes impact very strongly on cells and cytokines, (5) there is no antigen exposure level below which reduction of the antigen load alone initiates a flip back to the acute mode, and (6) adding healthy fibroblasts makes the transition from acute to chronic inflammation revertible, although (7) there is a window of antigen load where such a therapy cannot be effective. This suggests that triple therapies may be essential to overcome chronic inflammation. These may comprise (1) anti-immunoglobulin light chain peptides, (2) a temporarily reduced antigen load, and (3a) fibroblast repopulation or (3b) stem cell strategies.
      PubDate: 2020-02-14T00:00:00Z
       
  • Immunogenicity of Potential CD4+ and CD8+ T Cell Epitopes Derived From the
           Proteome of Leishmania braziliensis

    • Authors: Rafael de Freitas e Silva, Beatriz Coutinho de Oliveira, Ailton Alvaro da Silva, Maria Carolina Accioly Brelaz de Castro, Luiz Felipe Gomes Rebello Ferreira, Marcelo Zaldini Hernandes, Maria Edileuza Felinto de Brito, Osvaldo Pompílio de-Melo-Neto, Antônio Mauro Rezende, Valéria Rêgo Alves Pereira
      Abstract: Background: A safe and effective vaccine against human leishmaniasis still requires the identification of better antigens for immunization and adequate models to evaluate the immune response. To support vaccine development, this work tested the immunogenicity of 10 different peptides derived from the proteome of Leishmania braziliensis, which were selected by their in silico affinity to MHC complexes.Research design and Methods: Comparative cell proliferation assays were performed by culturing, in the presence of each peptide, PBMC cells from subclinical subjects (SC), cutaneous leishmaniasis patients with active disease (AD), post-treatment (PT) individuals, and healthy controls. Culture supernatants were then used for Th1, Th2, and Th17 cytokine measurements. Cells from selected PT samples were also used to assess the expression, by T cells, of the T-bet Th1 transcription factor.Results: A robust cell proliferation was observed for the SC group, for all the tested peptides. The levels of Th1 cytokines were peptide-dependent and had substantial variations between groups, where, for instance, IFN-γ and TNF levels were some of the highest, particularly on PT cultures, when compared to IL-2. On the other hand, Th2 cytokines displayed much less variation. IL-6 was the most abundant among all the evaluated cytokines while IL-4 and IL-10 could be found at much lower concentrations. IL-17 was also detected with variations in SC and AD groups. T-bet was up-regulated in CD4+ and CD8+ T cells from the PT group after stimulation with all peptides.Conclusions: The peptide epitopes can differentially stimulate cells from SC, AD, and PT individuals, leading to distinct immune responses.
      PubDate: 2020-02-14T00:00:00Z
       
  • Recombinant DnaK Orally Administered Protects Axenic European Sea Bass
           Against Vibriosis

    • Authors: Eamy Nursaliza Yaacob, Parisa Norouzitallab, Bruno G. De Geest, Aline Bajek, Kristof Dierckens, Peter Bossier, Daisy Vanrompay
      Abstract: Vibrio anguillarum causes high mortality in European sea bass (Dicentrarchus labrax) larviculture and is a hindering factor for successful sustainable aquaculture of this commercially valuable species. Priming of the innate immune system through administration of immunostimulants has become an important approach to control disease outbreaks in marine fish larviculture. This study was conducted to evaluate immunostimulation by Escherichia coli HSP70 (DnaK) in axenic European sea bass larvae in order to protect the larvae against vibriosis. DnaK stimulates the immune response in crustaceans and juvenile fish against bacterial infections. The use of axenic fish larvae allows to study immunostimulation in the absence of an interfering microbial community. At 7 days post-hatching, larvae received a single dose of alginate encapsulated recombinant DnaK. Two non-treated control groups in which animals either received empty alginate microparticles (C1) or no alginante microparticles (C2 and C3) were included in the study. Eighteen hours later, all larvae, except the ones from group C3 (non-infected control) were challenged with V. anguillarum (105 CFU, bath infection). Mortality was daily recorded until 120 h post infection and at 18, 24, and 36 h post infection, larvae were sampled for expression of immune related genes. Results showed that V. anguillarum induced an immune response in axenic sea bass larvae but that the innate immune response was incapable to protect the larvae against deadly septicaemic disease. In addition, we showed that administration of alginate encapsulated DnaK to axenic European sea bass larvae at DAH7 resulted in a significant, DnaK dose dependent, upreglation of immune sensor, regulatory and effector genes. Significant upregulation of cxcr4, cas1 and especially of hep and dic was correlated with significant higher survival rates in V. anguillarum infected larvae. In the future recombinant DnaK might perhaps be used as a novel immunostimulant in sea bass larviculture.
      PubDate: 2020-02-14T00:00:00Z
       
  • Targeting Extracellular Vesicles to the Arthritic Joint Using a Damaged
           Cartilage-Specific Antibody

    • Authors: Louise M. Topping, Bethan L. Thomas, Hefin I. Rhys, Jordi L. Tremoleda, Martyn Foster, Michael Seed, Mathieu-Benoit Voisin, Chiara Vinci, Hannah L. Law, Mauro Perretti, Lucy V. Norling, Helena S. Azevedo, Ahuva Nissim
      Abstract: The targeted delivery of therapies to diseased tissues offers a safe opportunity to achieve optimal efficacy while limiting systemic exposure. These considerations apply to many disease indications but are especially relevant for rheumatoid arthritis (RA), as RA is a systemic autoimmune disease which affects multiple joints. We have identified an antibody that is specific to damaged arthritic cartilage (anti-ROS-CII) that can be used to deliver treatments specifically to arthritic joints, yielding augmented efficacy in experimental arthritis. In the current study, we demonstrate that scaffolds enriched with bioactive payloads can be delivered precisely to an inflamed joint and achieve superior efficacy outcomes consistent with the pharmacological properties of these payloads. As a scaffold, we have used extracellular vesicles (EVs) prepared from human neutrophils (PMNs), which possess intrinsic anti-inflammatory properties and the ability to penetrate inflamed arthritic cartilage. EV fortified with anti-ROS-CII (EV/anti-ROS-CII) retained anti-ROS-CII specificity and bound exclusively to the damaged cartilage. Following systemic administration, EV/anti-ROS-CII (a) exhibited the ability to localize specifically in the arthritic joint in vivo and (b) was able to specifically target single (viral IL-10 or anti-TNF) or combined (viral IL-10 and anti-TNF) anti-inflammatory treatments to the arthritic joint, which accelerated attenuation of clinical and synovial inflammation. Overall, this study demonstrates the attainability of targeting a pro-resolving biological scaffold to the arthritic joint. The potential of targeting scaffolds such as EV, nanoparticles, or a combination thereof alongside combined therapeutics is paramount for designing systemically administered broad-spectrum of anti-inflammatory treatments.
      PubDate: 2020-02-14T00:00:00Z
       
  • NS5 Conservative Site Is Required for Zika Virus to Restrict the RIG-I
           Signaling

    • Authors: Aixin Li, Wenbiao Wang, Yingchong Wang, Keli Chen, Feng Xiao, Dingwen Hu, Lixia Hui, Weiyong Liu, Yuqian Feng, Geng Li, Qiuping Tan, Yingle Liu, Kailang Wu, Jianguo Wu
      Abstract: During host–virus co-evolution, cells develop innate immune systems to inhibit virus invasion, while viruses employ strategies to suppress immune responses and maintain infection. Here, we reveal that Zika virus (ZIKV), a re-emerging arbovirus causing public concerns and devastating complications, restricts host immune responses through a distinct mechanism. ZIKV nonstructural protein 5 (NS5) interacts with the host retinoic acid-inducible gene I (RIG-I), an essential signaling molecule for defending pathogen infections. NS5 subsequently represses K63-linked polyubiquitination of RIG-I, attenuates the phosphorylation and nuclear translocation of interferon regulatory factor 3 (IRF3), and inhibits the expression and production of interferon-β (IFN-β), thereby restricting the RIG-I signaling pathway. Interestingly, we demonstrate that the methyltransferase (MTase) domain of NS5 is required for the repression of RIG-I ubiquitination, IRF3 activation, and IFN-β production. Detailed studies further reveal that the conservative active site D146 of NS5 is critical for the suppression of the RIG-I signaling. Therefore, we uncover an essential role of NS5 conservative site D146 in ZIKV-mediated repression of innate immune system, illustrate a distinct mechanism by which ZIKV evades host immune responses, and discover a potential target for anti-viral infection.
      PubDate: 2020-02-14T00:00:00Z
       
  • Activation of the Kynurenine Pathway in Human Malignancies Can Be
           Suppressed by the Cyclin-Dependent Kinase Inhibitor Dinaciclib

    • Authors: Christin Riess, Björn Schneider, Hanna Kehnscherper, Julia Gesche, Nina Irmscher, Fatemeh Shokraie, Carl Friedrich Classen, Elisa Wirthgen, Grazyna Domanska, Annette Zimpfer, Daniel Strüder, Christian Junghanss, Claudia Maletzki
      Abstract: Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO2) are the key enzymes of tryptophan (TRP) metabolism in the kynurenine pathway (KP). Both enzymes function as indicators of immunosuppression and poor survival in cancer patients. Direct or indirect targeting of either of these substances seems thus reasonable to improve therapy options for patients. In this study, glioblastoma multiforme (GBM) as well as head and neck squamous cell carcinomas (HNSCC) were examined because of their different mechanisms of spontaneous and treatment-induced immune escape. Effects on gene expression and protein levels were examined. Accompanying assessment of TRP metabolites from treated GBM cell culture supernatants was conducted. Our results show a heterogeneous and inversely correlated expression profile of TRP-metabolizing genes among GBM and HNSCC cells, with low, but inducible IDO1 expression upon IFNγ treatment. TDO2 expression was higher in GBM cells, while genes encoding kynurenine aminotransferases were mainly confined to HNSCC cells. These data indicate that the KP is active in both entities, with however different enzymes involved in TRP catabolism. Upon treatment with Temozolomide, the standard of care for GBM patients, IDO1 was upregulated. Comparable, although less pronounced effects were seen in HNSCC upon Cetuximab and conventional drugs (i.e., 5-fluorouracil, Gemcitabine). Here, IDO1 and additional genes of the KP (KYAT1, KYAT2, and KMO) were induced. Vice versa, the novel yet experimental cyclin-dependent kinase inhibitor Dinaciclib suppressed KP in both entities. Our comprehensive data imply inhibition of the TRP catabolism by Dinaciclib, while conventional chemotherapeutics tend to activate this pathway. These data point to limitations of conventional therapy and highlight the potential of targeted therapies to interfere with the cells' metabolism more than anticipated.
      PubDate: 2020-02-14T00:00:00Z
       
  • Streptococcal Extracellular Membrane Vesicles Are Rapidly Internalized by
           Immune Cells and Alter Their Cytokine Release

    • Authors: Mina Mehanny, Marcus Koch, Claus-Michael Lehr, Gregor Fuhrmann
      Abstract: Extracellular vesicles are membranous structures shed by almost every living cell. Bacterial gram-negative outer membrane vesicles (OMVs) and gram-positive membrane vesicles (MVs) play important roles in adaptation to the surrounding environment, cellular components' exchange, transfer of antigens and virulence factors, and infection propagation. Streptococcus pneumoniae is considered one of the priority pathogens, with a global health impact due to the increase in infection burden and growing antibiotic resistance. We isolated MVs produced from the S. pneumoniae reference strain (R6) and purified them via size exclusion chromatography (SEC) to remove soluble protein impurities. We characterized the isolated MVs by nanoparticle tracking analysis (NTA) and measured their particle size distribution and concentration. Isolated MVs showed a mean particle size range of 130–160 nm and a particle yield of around 1012 particles per milliliter. Cryogenic transmission electron microscopy (cryo-TEM) images revealed a very heterogeneous nature of isolated MVs with a broad size range and various morphologies, arrangements, and contents. We incubated streptococcal MVs with several mammalian somatic cells, namely, human lung epithelial A549 and human keratinocytes HaCaT cell lines, and immune cells including differentiated macrophage-like dTHP-1 and murine dendritic DC2.4 cell lines. All cell lines displayed excellent viability profile and negligible cytotoxicity after 24-h incubation with MVs at concentrations reaching 106 MVs per cell (somatic cells) and 105 MVs per cell (immune cells). We evaluated the uptake of fluorescently labeled MVs into these four cell lines, using flow cytometry and confocal microscopy. Dendritic cells demonstrated prompt uptake after 30-min incubation, whereas other cell lines showed increasing uptake after 2-h incubation and almost complete colocalization/internalization of MVs after only 4-h incubation. We assessed the influence of streptococcal MVs on antigen-presenting cells, e.g., dendritic cells, using enzyme-linked immunosorbent assay (ELISA) and observed enhanced release of tumor necrosis factor (TNF)-α, a slight increase of interleukin (IL)-10 secretion, and no detectable effect on IL-12. Our study provides a better understanding of gram-positive streptococcal MVs and shows their potential to elicit a protective immune response. Therefore, they could offer an innovative avenue for safe and effective cell-free vaccination against pneumococcal infections.
      PubDate: 2020-02-14T00:00:00Z
       
  • Fc Receptor-Like 6 (FCRL6) Discloses Progenitor B Cell Heterogeneity That
           Correlates With Pre-BCR Dependent and Independent Pathways of Natural
           Antibody Selection

    • Authors: Kazuhito Honjo, Woong-Jai Won, Rodney G. King, Lara Ianov, David K. Crossman, Juliet L. Easlick, Mikhail A. Shakhmatov, Mohamed Khass, Andre M. Vale, Robert P. Stephan, Ran Li, Randall S. Davis
      Abstract: B-1a cells produce “natural” antibodies (Abs) to neutralize pathogens and clear neo self-antigens, but the fundamental selection mechanisms that shape their polyreactive repertoires are poorly understood. Here, we identified a B cell progenitor subset defined by Fc receptor-like 6 (FCRL6) expression, harboring innate-like defense, migration, and differentiation properties conducive for natural Ab generation. Compared to FCRL6− pro B cells, the repressed mitotic, DNA damage repair, and signaling activity of FCRL6+ progenitors, yielded VH repertoires with biased distal Ighv segment accessibility, constrained diversity, and hydrophobic and charged CDR-H3 sequences. Beyond nascent autoreactivity, VH11 productivity, which predominates phosphatidylcholine-specific B-1a B cell receptors (BCRs), was higher for FCRL6+ cells as was pre-BCR formation, which was required for Myc induction and VH11, but not VH12, B-1a development. Thus, FCRL6 revealed unexpected heterogeneity in the developmental origins, regulation, and selection of natural Abs at the pre-BCR checkpoint with implications for autoimmunity and lymphoproliferative disorders.
      PubDate: 2020-02-14T00:00:00Z
       
  • A Tissue-Specific Rhythmic Recruitment Pattern of Leukocyte Subsets

    • Authors: Yinglin Yuan, Shengwang Wu, Weiwei Li, Wenyan He
      Abstract: The circulating of leukocytes in the vasculature to reach various organs is a crucial step that allows them to perform their function. With a sequence of interaction with the endothelial cells, the leukocytes emigrate from the circulation either by firm attachment to vascular beds or by trafficking into the tissues. Recent findings reveal that the leukocyte recruitment shows time as well as tissue specificity depending on the cell type and homing location. This spatiotemporal distribution of leukocyte subsets is driven by the circadian expression of pro-migratory molecules expressed on the leukocytes and the endothelium. Both the systemic circadian signals and the cell's intrinsic molecule clock contribute to the oscillatory expression of pro-migratory molecules. The rhythmic recruitment of leukocytes plays an important role in the time-dependency of immune responses. It also helps to update blood components and maintain the tissue circadian microenvironment. In this review, we discuss the current knowledge about the mechanisms of the circadian system regulating the leukocyte rhythmic migration, the recruitment pattern of leukocyte subsets into different tissue/organs, and the time-dependent effects behind this process.
      PubDate: 2020-02-14T00:00:00Z
       
  • The Imbalance of Circulating Follicular Helper T Cells and Follicular
           Regulatory T Cells Is Associated With Disease Activity in Patients With
           Ulcerative Colitis

    • Authors: Yan Long, Changsheng Xia, Lijuan Xu, Caoyi Liu, Chunhong Fan, Huizhang Bao, Xiaotao Zhao, Chen Liu
      Abstract: Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colon and rectum, in which the abnormality of B cells is involved in both its pathogenesis and progression. Follicular helper T cells (TFH) play an important role in assisting the immune function of human B cells in germinal centers, and follicular regulatory T cells (TFR) have the function of inhibiting TFH and germinal center B cell responses. The significance of circulating TFH and TFR in ulcerative colitis (UC) remains unclear. We analyzed peripheral blood of active and stable remission UC patients and found that circulating TFR was significantly decreased while TFH was increased in active UC patients. As to TFH subsets, TFH2 was elevated while TFH17 was decreased in active UC, with IL-4/IL-17A secretion enhanced. Helios+ and CD45RA−FoxP3high TFR cells were decreased while CD226+ and CD45RA+FoxP3int TFR cells were increased in active UC patients. The levels of new memory B cells, plasmablasts and serum IgG were significantly increased in active UC patients, and were positively correlated with TFH and TFH2, and negatively correlated with TFR. Serum CRP and Mayo Clinic scores were positively correlated with TFH and TFH2 but negatively correlated with TFR. Serum IL-12 and IL-21 were up-regulated while IL-10 was down-regulated in active UC. To conclude, an imbalance of circulating TFH and TFR cells is associated with disease activity in UC patients. Our results suggest a new mechanism for TFH and TFR imbalance in the pathogenesis of UC, providing a new perspective for theoretical research and therapeutic strategies for UC.
      PubDate: 2020-02-14T00:00:00Z
       
  • IL-17A Modulates Peritoneal Macrophage Recruitment and M2 Polarization in
           Endometriosis

    • Authors: Jessica E. Miller, Soo Hyun Ahn, Ryan M. Marks, Stephany P. Monsanto, Asgerally T. Fazleabas, Madhuri Koti, Chandrakant Tayade
      Abstract: Endometriosis is a debilitating gynecological disease characterized by the extrauterine presence of endometrial-like tissues located on the peritoneal membrane and organs of the pelvic cavity. Notably, dysfunctional immune activation in women with endometriosis could also contribute to the development of disease. In particular, alternatively activated (M2) peritoneal macrophages are shown to aid peritoneal lesion development by promoting remodeling of extracellular matrix and neovascularization of lesions. However, the stimuli responsible for polarizing M2 macrophages in endometriosis remain elusive. Interleukin-17A (IL-17A) can induce M2 macrophage polarization in other disease models and IL-17A is elevated in the plasma and endometriotic lesions of women with endometriosis. In this study, we investigated whether IL-17A could induce macrophage recruitment and M2 polarization, while promoting endometriotic lesion growth through enhanced vascularization. By utilizing a co-culture of macrophage-like THP-1 cells with an endometriotic epithelial cell line, our in vitro results suggest that IL-17A indirectly induces M2 markers CCL17 and CD206 by interacting with endometriotic epithelial cells. Further, in a syngeneic mouse model of endometriosis, IL-17A treatment increased macrophages in the peritoneum, which were also M2 in phenotype. However, IL-17A treatment did not augment proliferation or vascularization of the lesion in the study time frame. These findings suggest that IL-17A may be a stimulus inducing the pathogenic polarization of macrophages into the M2 phenotype by first acting on the endometriotic lesion itself.
      PubDate: 2020-02-14T00:00:00Z
       
  • Neoantigens in Hematologic Malignancies

    • Authors: Melinda A. Biernacki, Marie Bleakley
      Abstract: T cell cancer neoantigens are created from peptides derived from cancer-specific aberrant proteins, such as mutated and fusion proteins, presented in complex with human leukocyte antigens on the cancer cell surface. Because expression of the aberrant target protein is exclusive to malignant cells, immunotherapy directed against neoantigens should avoid “on-target, off-tumor” toxicity. The efficacy of neoantigen vaccines in melanoma and glioblastoma and of adoptive transfer of neoantigen-specific T cells in epithelial tumors indicates that neoantigens are valid therapeutic targets. Improvements in sequencing technology and innovations in antigen discovery approaches have facilitated the identification of neoantigens. In comparison to many solid tumors, hematologic malignancies have few mutations and thus fewer potential neoantigens. Despite this, neoantigens have been identified in a wide variety of hematologic malignancies. These include mutated nucleophosmin1 and PML-RARA in acute myeloid leukemia, ETV6-RUNX1 fusions and other mutated proteins in acute lymphoblastic leukemia, BCR-ABL1 fusions in chronic myeloid leukemia, driver mutations in myeloproliferative neoplasms, immunoglobulins in lymphomas, and proteins derived from patient-specific mutations in chronic lymphoid leukemias. We will review advances in the field of neoantigen discovery, describe the spectrum of identified neoantigens in hematologic malignancies, and discuss the potential of these neoantigens for clinical translation.
      PubDate: 2020-02-14T00:00:00Z
       
  • The Irony of Humanization: Alemtuzumab, the First, But One of the Most
           Immunogenic, Humanized Monoclonal Antibodies

    • Authors: David Baker, Liaqat Ali, Gauri Saxena, Gareth Pryce, Meleri Jones, Klaus Schmierer, Gavin Giovannoni, Sharmilee Gnanapavan, Kathleen C. Munger, Lawrence Samkoff, Andrew Goodman, Angray S. Kang
      Abstract: Alemtuzumab was designed to reduce the immunogenicity of the parent CD52-specific rat immunoglobulin. Although originally marketed for use in cancer (Mabcampath®), alemtuzumab is currently licensed and formulated for the treatment of relapsing multiple sclerosis (Lemtrada®). Perhaps due to its history as the first humanized antibody, the potential of immunogenicity of the molecule has been considered inconsequential, and anti-drug antibodies (ADA) responses were similarly reported as being clinically insignificant. Nonetheless, despite humanization and depletion of peripheral T and B cells, alemtuzumab probably generates the highest frequency of binding and neutralizing ADA of all humanized antibodies currently in clinical use, and they occur rapidly in a large majority of people with MS (pwMS) on alemtuzumab treatment. These ADA appear to be an inherent issue of the biology of the molecule—and more importantly, the target—such that avoidance of immunogenicity-related effects has been facilitated by the dosing schedule used in clinical practice. At the population level this enables the drug to work in most pwMS, but in some individuals, as we show here, antibody neutralization appears to be sufficiently severe to reduce efficacy and allow disease breakthrough. It is therefore imperative that efficacy of lymphocyte depletion and the anti-drug response is monitored in people requiring additional cycles of treatment, notably following disease breakthrough. This may help inform whether to re-treat or to switch to another disease-modifying treatment.
      PubDate: 2020-02-14T00:00:00Z
       
  • Maternal-Fetal Interplay in Zika Virus Infection and Adverse Perinatal
           Outcomes

    • Authors: Franciane Mouradian Emidio Teixeira, Anna Julia Pietrobon, Luana de Mendonça Oliveira, Luanda Mara da Silva Oliveira, Maria Notomi Sato
      Abstract: During pregnancy, the organization of complex tolerance mechanisms occurs to assure non-rejection of the semiallogeneic fetus. Pregnancy is a period of vulnerability to some viral infections, mainly during the first and second trimesters, that may cause congenital damage to the fetus. Recently, Zika virus (ZIKV) infection has gained great notoriety due to the occurrence of congenital ZIKV syndrome, characterized by fetal microcephaly, which results from the ability of ZIKV to infect placental cells and neural precursors in the fetus. Importantly, in addition to the congenital effects, studies have shown that perinatal ZIKV infection causes a number of disorders, including maculopapular rash, conjunctivitis, and arthralgia. In this paper, we contextualize the immunological aspects involved in the maternal-fetal interface and vulnerability to ZIKV infection, especially the alterations resulting in perinatal outcomes. This highlights the need to develop protective maternal vaccine strategies or interventions that are capable of preventing fetal or even neonatal infection.
      PubDate: 2020-02-14T00:00:00Z
       
  • The Methyl-CpG-Binding Protein Mbd2 Regulates Susceptibility to
           Experimental Colitis via Control of CD11c+ Cells and Colonic Epithelium

    • Authors: Gareth-Rhys Jones, Sheila L. Brown, Alexander T. Phythian-Adams, Alasdair C. Ivens, Peter C. Cook, Andrew S. MacDonald
      Abstract: Methyl-CpG-binding domain-2 (Mbd2) acts as an epigenetic regulator of gene expression, by linking DNA methylation to repressive chromatin structure. Although Mbd2 is widely expressed in gastrointestinal immune cells and is implicated in regulating intestinal cancer, anti-helminth responses and colonic inflammation, the Mbd2-expressing cell types that control these responses are incompletely defined. Indeed, epigenetic control of gene expression in cells that regulate intestinal immunity is generally poorly understood, even though such mechanisms may explain the inability of standard genetic approaches to pinpoint the causes of conditions like inflammatory bowel disease. In this study we demonstrate a vital role for Mbd2 in regulating murine colonic inflammation. Mbd2−/− mice displayed dramatically worse pathology than wild type controls during dextran sulfate sodium (DSS) induced colitis, with increased inflammatory (IL-1β+) monocytes. Profiling of mRNA from innate immune and epithelial cell (EC) populations suggested that Mbd2 suppresses inflammation and pathology via control of innate-epithelial cell crosstalk and T cell recruitment. Consequently, restriction of Mbd2 deficiency to CD11c+ dendritic cells and macrophages, or to ECs, resulted in increased DSS colitis severity. Our identification of this dual role for Mbd2 in regulating the inflammatory capacity of both CD11c+ cells and ECs highlights how epigenetic control mechanisms may limit intestinal inflammatory responses.
      PubDate: 2020-02-14T00:00:00Z
       
  • Editorial: Immunoregulatory Mechanisms of Interferon

    • Authors: Claudia U. Duerr, Jörg H. Fritz
      PubDate: 2020-02-14T00:00:00Z
       
  • Key Aspects of the Immunobiology of Haploidentical Hematopoietic Cell
           Transplantation

    • Authors: Susanne H. C. Baumeister, Benedetta Rambaldi, Roman M. Shapiro, Rizwan Romee
      Abstract: Hematopoietic stem cell transplantation from a haploidentical donor is increasingly used and has become a standard donor option for patients lacking an appropriately matched sibling or unrelated donor. Historically, prohibitive immunological barriers resulting from the high degree of HLA-mismatch included graft-vs.-host disease (GVHD) and graft failure. These were overcome with increasingly sophisticated strategies to manipulate the sensitive balance between donor and recipient immune cells. Three different approaches are currently in clinical use: (a) ex vivo T-cell depletion resulting in grafts with defined immune cell content (b) extensive immunosuppression with a T-cell replete graft consisting of G-CSF primed bone marrow and PBSC (GIAC) (c) T-cell replete grafts with post-transplant cyclophosphamide (PTCy). Intriguing studies have recently elucidated the immunologic mechanisms by which PTCy prevents GVHD. Each approach uniquely affects post-transplant immune reconstitution which is critical for the control of post-transplant infections and relapse. NK-cells play a key role in haplo-HCT since they do not mediate GVHD but can successfully mediate a graft-vs.-leukemia effect. This effect is in part regulated by KIR receptors that inhibit NK cell cytotoxic function when binding to the appropriate HLA-class I ligands. In the context of an HLA-class I mismatch in haplo-HCT, lack of inhibition can contribute to NK-cell alloreactivity leading to enhanced anti-leukemic effect. Emerging work reveals immune evasion phenomena such as copy-neutral loss of heterozygosity of the incompatible HLA alleles as one of the major mechanisms of relapse. Relapse and infectious complications remain the leading causes impacting overall survival and are central to scientific advances seeking to improve haplo-HCT. Given that haploidentical donors can typically be readily approached to collect additional stem- or immune cells for the recipient, haplo-HCT represents a unique platform for cell- and immune-based therapies aimed at further reducing relapse and infections. The rapid advancements in our understanding of the immunobiology of haplo-HCT are therefore poised to lead to iterative innovations resulting in further improvement of outcomes with this compelling transplant modality.
      PubDate: 2020-02-14T00:00:00Z
       
  • Rheumatoid Arthritis Patients, Both Newly Diagnosed and Methotrexate
           Treated, Show More DNA Methylation Differences in CD4+ Memory Than in CD4+
           Naïve T Cells

    • Authors: Kari Guderud, Line H. Sunde, Siri T. Flåm, Marthe T. Mæhlen, Maria D. Mjaavatten, Siri Lillegraven, Anna-Birgitte Aga, Ida M. Evenrød, Ellen S. Norli, Bettina K. Andreassen, Sören Franzenburg, Andre Franke, Espen A. Haavardsholm, Simon Rayner, Kristina Gervin, Benedicte A. Lie
      Abstract: Background: Differences in DNA methylation have been reported in B and T lymphocyte populations, including CD4+ T cells, isolated from rheumatoid arthritis (RA) patients when compared to healthy controls. CD4+ T cells are a heterogeneous cell type with subpopulations displaying distinct DNA methylation patterns. In this study, we investigated DNA methylation using reduced representation bisulfite sequencing in two CD4+ T cell populations (CD4+ memory and naïve cells) in three groups: newly diagnosed, disease modifying antirheumatic drugs (DMARD) naïve RA patients (N = 11), methotrexate (MTX) treated RA patients (N = 18), and healthy controls (N = 9) matched for age, gender and smoking status.Results: Analyses of these data revealed significantly more differentially methylated positions (DMPs) in CD4+ memory than in CD4+ naïve T cells (904 vs. 19 DMPs) in RA patients compared to controls. The majority of DMPs (72%) identified in newly diagnosed and DMARD naïve RA patients with active disease showed increased DNA methylation (39 DMPs), whereas most DMPs (80%) identified in the MTX treated RA patients in remission displayed decreased DNA methylation (694 DMPs). Interestingly, we also found that about one third of the 101 known RA risk loci overlapped (±500 kb) with the DMPs. Notably, introns of the UBASH3A gene harbor both the lead RA risk SNP and two DMPs in CD4+ memory T cells.Conclusion: Our results suggest that RA associated DNA methylation differences vary between the two T cell subsets, but are also influenced by RA characteristics such as disease activity, disease duration and/or MTX treatment.
      PubDate: 2020-02-14T00:00:00Z
       
  • Malnutrition Decreases Antibody Secreting Cell Numbers Induced by an Oral
           Attenuated Human Rotavirus Vaccine in a Human Infant Fecal Microbiota
           Transplanted Gnotobiotic Pig Model

    • Authors: Husheem Michael, Stephanie N. Langel, Ayako Miyazaki, Francine C. Paim, Juliet Chepngeno, Moyasar A. Alhamo, David D. Fischer, Vishal Srivastava, Dipak Kathayat, Loic Deblais, Gireesh Rajashekara, Linda J. Saif, Anastasia N. Vlasova
      Abstract: Human rotavirus (HRV) is a leading cause of morbidity and mortality in children, especially in developing countries. Malnutrition is prevalent in these countries, which may contribute to the decreased oral vaccine efficacy, posing a concern for global health. Neonatal gnotobiotic (Gn) pigs closely resemble human infants in their anatomy, physiology, and outbred status and are a unique model to investigate malnutrition, oral live attenuated HRV (AttHRV) vaccination, and subsequent virulent HRV (VirHRV) challenge. We evaluated the impact of malnutrition on AttHRV vaccine efficacy and B cell immune responses in neonatal germfree (GF) or Gn pigs transplanted with human infant fecal microbiota (HIFM). Pigs were fed either deficient or sufficient bovine milk diets. Malnutrition did not significantly affect the serum and intestinal contents total or HRV-specific IgG and IgA antibody titers pre VirHRV challenge. However, HRV-specific IgG and IgA antibody secreting cells (ASCs) were reduced in blood or intestinal tissues following AttHRV vaccination and pre VirHRV challenge in deficient HIFM transplanted pigs. Furthermore, post-VirHRV challenge, deficient HIFM pigs had decreased total Ig and HRV-specific IgG and IgA antibody titers in serum or intestinal contents, in addition to decreased HRV-specific IgG and IgA ASCs in blood and ileum, compared with sufficient HIFM pigs. Our results indicate that deficient diet impairs B cell mucosal, and systemic immune responses following HRV vaccination, and challenge. The impaired immune responses contributed to the decreased protective efficacy of the AttHRV vaccine, suggesting that malnutrition may significantly reduce the effectiveness of oral HRV vaccines in children in developing countries.
      PubDate: 2020-02-14T00:00:00Z
       
  • CD1b Tetramers Broadly Detect T Cells That Correlate With Mycobacterial
           Exposure but Not Tuberculosis Disease State

    • Authors: Kattya Lopez, Sarah K. Iwany, Sara Suliman, Josephine F. Reijneveld, Tonatiuh A. Ocampo, Judith Jimenez, Roger Calderon, Leonid Lecca, Megan B. Murray, D. Branch Moody, Ildiko Van Rhijn
      Abstract: The non-polymorphic nature of CD1 proteins creates a situation in which T cells with invariant T cell receptors (TCRs), like CD1d-specific NKT cells, are present in all humans. CD1b is an abundant protein on human dendritic cells that presents M. tuberculosis (Mtb) lipid antigens to T cells. Analysis of T cell clones suggested that semi-invariant TCRs exist in the CD1b system, but their prevalence in humans is not known. Here we used CD1b tetramers loaded with mycolic acid or glucose monomycolate to study polyclonal T cells from 150 Peruvian subjects. We found that CD1b tetramers loaded with mycolic acid or glucose monomycolate antigens stained TRAV1-2+ GEM T cells or TRBV4-1+ LDN5-like T cells in the majority of subjects tested, at rates ~10-fold lower than NKT cells. Thus, GEM T cells and LDN5-like T cells are a normal part of the human immune system. Unlike prior studies measuring MHC- or CD1b-mediated activation, this large-scale tetramer study found no significant differences in rates of CD1b tetramer-mycobacterial lipid staining of T cells among subjects with Mtb exposure, latent Mtb infection or active tuberculosis (TB) disease. In all subjects, including “uninfected” subjects, CD1b tetramer+ T cells expressed memory markers at high levels. However, among controls with lower mycobacterial antigen exposure in Boston, we found significantly lower frequencies of T cells staining with CD1b tetramers loaded with mycobacterial lipids. These data link CD1b-specific T cell detection to mycobacterial exposure, but not TB disease status, which potentially explains differences in outcomes among CD1-based clinical studies, which used control subjects with low Mtb exposure.
      PubDate: 2020-02-14T00:00:00Z
       
 
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