دورية أكاديمية
CD8+ lymphocytes are critical for early control of tuberculosis in macaques.
العنوان: | CD8+ lymphocytes are critical for early control of tuberculosis in macaques. |
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المؤلفون: | Winchell CG; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA, USA., Nyquist SK; Program in Computational and Systems Biology, Massachusetts Institute of Technology , Cambridge, MA, USA.; Broad Institute, Harvard University and Massachusetts Institute of Technology , Cambridge, MA, USA.; Department of Chemistry, Institute for Medical Engineering and Science, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.; Computer Science and Artificial Intelligence Laboratory and Department of Mathematics, MIT, Cambridge, MA, USA., Chao MC; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA., Maiello P; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA, USA., Myers AJ; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA, USA., Hopkins F; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA., Chase M; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA., Gideon HP; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA, USA., Patel KV; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA, USA., Bromley JD; Program in Computational and Systems Biology, Massachusetts Institute of Technology , Cambridge, MA, USA.; Broad Institute, Harvard University and Massachusetts Institute of Technology , Cambridge, MA, USA.; Department of Chemistry, Institute for Medical Engineering and Science, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.; Computer Science and Artificial Intelligence Laboratory and Department of Mathematics, MIT, Cambridge, MA, USA., Simonson AW; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA, USA., Floyd-O'Sullivan R; Broad Institute, Harvard University and Massachusetts Institute of Technology , Cambridge, MA, USA.; Department of Chemistry, Institute for Medical Engineering and Science, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA., Wadsworth M; Broad Institute, Harvard University and Massachusetts Institute of Technology , Cambridge, MA, USA.; Department of Chemistry, Institute for Medical Engineering and Science, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA., Rosenberg JM; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA., Uddin R; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA., Hughes T; Broad Institute, Harvard University and Massachusetts Institute of Technology , Cambridge, MA, USA.; Department of Chemistry, Institute for Medical Engineering and Science, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA., Kelly RJ; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA, USA., Griffo J; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Tomko J; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA, USA., Klein E; Division of Laboratory Animal Research, University of Pittsburgh, Pittsburgh, PA, USA., Berger B; Broad Institute, Harvard University and Massachusetts Institute of Technology , Cambridge, MA, USA.; Computer Science and Artificial Intelligence Laboratory and Department of Mathematics, MIT, Cambridge, MA, USA., Scanga CA; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA, USA., Mattila J; Department of Infectious Disease and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA., Fortune SM; Broad Institute, Harvard University and Massachusetts Institute of Technology , Cambridge, MA, USA.; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.; Ragon Institute of MGH, MIT, and Harvard , Cambridge, MA, USA., Shalek AK; Broad Institute, Harvard University and Massachusetts Institute of Technology , Cambridge, MA, USA.; Department of Chemistry, Institute for Medical Engineering and Science, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.; Computer Science and Artificial Intelligence Laboratory and Department of Mathematics, MIT, Cambridge, MA, USA.; Ragon Institute of MGH, MIT, and Harvard , Cambridge, MA, USA., Lin PL; Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA, USA.; Department of Pediatrics, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Flynn JL; Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Center for Vaccine Research, University of Pittsburgh School of Medicine , Pittsburgh, PA, USA. |
المصدر: | The Journal of experimental medicine [J Exp Med] 2023 Dec 04; Vol. 220 (12). Date of Electronic Publication: 2023 Oct 16. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 2985109R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1540-9538 (Electronic) Linking ISSN: 00221007 NLM ISO Abbreviation: J Exp Med Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: New York, NY : Rockefeller University Press |
مواضيع طبية MeSH: | Tuberculosis*/microbiology , Mycobacterium tuberculosis*, Animals ; Macaca ; CD8-Positive T-Lymphocytes ; Granuloma ; CD4-Positive T-Lymphocytes |
مستخلص: | The functional role of CD8+ lymphocytes in tuberculosis remains poorly understood. We depleted innate and/or adaptive CD8+ lymphocytes in macaques and showed that loss of all CD8α+ cells (using anti-CD8α antibody) significantly impaired early control of Mycobacterium tuberculosis (Mtb) infection, leading to increased granulomas, lung inflammation, and bacterial burden. Analysis of barcoded Mtb from infected macaques demonstrated that depletion of all CD8+ lymphocytes allowed increased establishment of Mtb in lungs and dissemination within lungs and to lymph nodes, while depletion of only adaptive CD8+ T cells (with anti-CD8β antibody) worsened bacterial control in lymph nodes. Flow cytometry and single-cell RNA sequencing revealed polyfunctional cytotoxic CD8+ lymphocytes in control granulomas, while CD8-depleted animals were unexpectedly enriched in CD4 and γδ T cells adopting incomplete cytotoxic signatures. Ligand-receptor analyses identified IL-15 signaling in granulomas as a driver of cytotoxic T cells. These data support that CD8+ lymphocytes are required for early protection against Mtb and suggest polyfunctional cytotoxic responses as a vaccine target. (© 2023 Winchell et al.) |
التعليقات: | Comment in: J Exp Med. 2023 Dec 4;220(12):. (PMID: 37917028) |
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معلومات مُعتمدة: | KL2 TR002542 United States TR NCATS NIH HHS; 75N93019C00071 United States AI NIAID NIH HHS; P40 OD028116 United States OD NIH HHS; T32 AI089443 United States AI NIAID NIH HHS; P30 AI060354 United States AI NIAID NIH HHS; R56 AI139053 United States AI NIAID NIH HHS; K12 HL143886 United States HL NHLBI NIH HHS; U24 AI126683 United States AI NIAID NIH HHS |
تواريخ الأحداث: | Date Created: 20231016 Date Completed: 20231023 Latest Revision: 20240423 |
رمز التحديث: | 20240423 |
مُعرف محوري في PubMed: | PMC10579699 |
DOI: | 10.1084/jem.20230707 |
PMID: | 37843832 |
قاعدة البيانات: | MEDLINE |
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