@article{ade9e4186e8142adbf9f8d794c4d0955,
title = "TRAV1-2+ CD8+ T-cells including oligoconal expansions of MAIT cells are enriched in the airways in human tuberculosis",
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.",
author = "Wong, {Emily B.} and Gold, {Marielle C.} and Meermeier, {Erin W.} and Xulu, {Bongiwe Z.} and Sharon Khuzwayo and Sullivan, {Zuri A.} and Eisa Mahyari and Zoe Rogers and H{\'e}nrik Kl{\o}verpris and Sharma, {Prabhat K.} and Worley, {Aneta H.} and Umesh Lalloo and Prinita Baijnath and Anish Ambaram and Leon Naidoo and Moosa Suleman and Rajhmun Madansein and McLaren, {James E.} and Kristin Ladell and Miners, {Kelly L.} and Price, {David A.} and Behar, {Samuel M.} and Morten Nielsen and Kasprowicz, {Victoria O.} and Alasdair Leslie and Bishai, {William R.} and Thumbi Ndung{\textquoteright}u and Lewinsohn, {David M.}",
note = "Funding Information: We would like to thank Hollis Shen of the AHRI Immunology Core for technical assistance, Kamini Gounder for HLA genotyping, James McCluskey and his laboratory for use of the MR1 tetramers, the Pacific Northwest Transplant Bank for ongoing provision of research tissue, the HIV Pathogenesis Programme Processing Laboratory staff, the AHRI Clinical Core, the staff of Inkosi Albert Luthuli Central Hospital, and the study participants. This work was funded in part by a Burroughs-Wellcome Fund/American Society of Tropical Medicine and Hygiene fellowship (EBW), a Fulbright Award (ZAS), the National Institutes of Health (grants T32 AI007387 and K08 AI118538 to E.B.W., grant R01AI078965 to M.C.G., grant R01AI048090 to D.M.L., grants R01AI37856 and R01AI97138 to W.R.B., grant R01AI106725 to S.M.B.), the National Institute of Allergy and Infectious Diseases Mucosal Immunology Studies Team (grant U01AI09577 to M.C.G. and D.M.L.), and Merit Review Awards # I01 BX001231 and I01 BX000533 from the United States Department of Veterans Affairs (VA) Biomedical Laboratory Research and Development, supported by use of the facilities and resources at the VA Portland Health Care System. T.N. received funding from the South African DST/NRF Research Chairs Initiative and the Victor Daitz Foundation. D.A.P. is a Wellcome Trust Senior Investigator. Collection of samples from the iThimba Cohort was supported by the Harvard University Center for AIDS Research (grant P30 AI060354). Research reported in this publication was supported by the Strategic Health Innovation Partnerships (SHIP) Unit of the South African Medical Research Council (SA MRC) with funds received from the South African Department of Science and Technology as part of a bilateral research collaboration agreement with the Government of India; and through a SA MRC Collaborating Centre (ACT4TB/HIV).This work was also supported in part through the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative [grant # DEL-15-006]. The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS){\textquoteright}s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa{\textquoteright}s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [grant # 107752/Z/15/Z] and the UK government. Open access publication of this article has been made possible through support from the Victor Daitz Information Gateway, an initiative of the Victor Daitz Foundation and the University of KwaZulu-Natal. The views expressed in this publication are those of the authors and do not represent the views of the Unites States Department of Veterans Affairs, the United States Government, AAS, NEPAD Agency, Wellcome Trust or the UK government. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s42003-019-0442-2",
language = "English (US)",
volume = "2",
journal = "Communications Biology",
issn = "2399-3642",
publisher = "Springer Nature",
number = "1",
}