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Commun Biol. 2019 Jun 5;2:203. doi: 10.1038/s42003-019-0442-2. eCollection 2019.

TRAV1-2+ CD8+ T-cells including oligoconal expansions of MAIT cells are enriched in the airways in human tuberculosis.

Author information

1
1Africa Health Research Institute, KwaZulu-Natal, South Africa.
2
2Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA USA.
3
3Harvard Medical School, Boston, MA USA.
4
4Division of Infection and Immunity, University College London, London, UK.
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5Department of Pulmonary & Critical Care Medicine, Oregon Health & Science University, Portland, OR USA.
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6VA Portland Health Care System, Portland, OR USA.
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7Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR USA.
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8Division of Bioinformatics and Computational Biology (BCB), Department of Medical Informatics and Clinical Epidemiology (DMICE), Oregon Health & Science University, Portland, OR USA.
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9Institute for Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
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10Durban University of Technology, Durban, South Africa.
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Department of Pulmonology, Inkosi Albert Luthuli Hospital, Durban, South Africa.
12
12Department of Pulmonology & Critical Care, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
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13Department of Cardiothoracic Surgery, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
14
14Centre for AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa.
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15Institute of Infection & Immunity, Cardiff University School of Medicine, Cardiff, Wales UK.
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16Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland USA.
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17Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA USA.
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18Center for Biological Sequence Analysis, Department of Bio and Health Informatics, Technical University of Denmark, Lyngby, Denmark.
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19Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, Buenos Aires, Argentina.
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20HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
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21The Ragon Institute of MGH, MIT, and Harvard, Harvard Medical School, Cambridge, MA USA.
22
22Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD USA.
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23Max Planck Institute for Infection Biology, Berlin, Germany.
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Contributed equally

Abstract

Mucosal-associated invariant T (MAIT) cells typically express a TRAV1-2+ semi-invariant TCRα that enables recognition of bacterial, mycobacterial, and fungal riboflavin metabolites presented by MR1. MAIT cells are associated with immune control of bacterial and mycobacterial infections in murine models. Here, we report that a population of pro-inflammatory TRAV1-2+ CD8+ T cells are present in the airways and lungs of healthy individuals and are enriched in bronchoalveolar fluid of patients with active pulmonary tuberculosis (TB). High-throughput T cell receptor analysis reveals oligoclonal expansions of canonical and donor-unique TRAV1-2+ MAIT-consistent TCRα sequences within this population. Some of these cells demonstrate MR1-restricted mycobacterial reactivity and phenotypes suggestive of MAIT cell identity. These findings demonstrate enrichment of TRAV1-2+ CD8+ T cells with MAIT or MAIT-like features in the airways during active TB and suggest a role for these cells in the human pulmonary immune response to Mycobacterium tuberculosis.

KEYWORDS:

Mucosal immunology; T-cell receptor; Tuberculosis

Conflict of interest statement

Competing interestsThe authors declare no competing interests.

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