Article abstracts

Main reference:

A population of pro-inflammatory TRAV1-2+ CD8+ T-cells including oligoconal expansions of MAIT cells is enriched in the airways in human tuberculosis
Emily B. Wong 1,2, Marielle C. Gold3,4,5, Umesh Lalloo6, Bongiwe Z. Xulu1, Zuri A. Sullivan1, Zoe Rogers1, Henrik Kloverpris1, Erin W. Meermeier5, Prabhat K. Sharma4, Aneta H. Worley 3,4, Prinita Baijnath6, Anish Ambaram6, Leon Naidoo6, Rajhmun Madansein7, James E. McLaren8, David A. Price 8,9, Samuel M. Behar10, Morten Nielsen11, Victoria O. Kasprowicz1,12,13, Alasdair Leslie1, Thumbi Ndung'u1,12,13,14, William R. Bishai15, David M. Lewinsohn3,4,5.


Mucosal-associated invariant T (MAIT) cells typically express a TRAV1-2+ semi-invariant TCR 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 TCR# 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. 1KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa
2Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA
3Department of Pulmonary & Critical Care Medicine, Oregon Health & Science University, Portland, OR, USA
4 VA Portland Health Care Center, Portland, OR, USA
5Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon 97239, USA
6Department of Pulmonology and Critical Care, Nelson Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa
7Department of Cardiothoracic Surgery, Nelson Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa
8Institute of Infection & Immunity, Cardiff University School of Medicine, Cardiff, Wales, UK
9Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
10Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA
11Center for Biological Sequence Analysis, BioCentrum-DTU, Technical University of Denmark, Lyngby, Denmark
12 HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa
13 The Ragon Institute of MGH, MIT, and Harvard, Harvard Medical School, Cambridge, MA
14Max Planck Institute for Infection Biology, Berlin, Germany
15Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD