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

Emily B. Wong, Marielle Gold, Erin W. Meermeier, Bongiwe Z. Xulu, Sharon Khuzwayo, Zuri A. Sullivan, Eisa Mahyari, Zoe Rogers, Hénrik Kløverpris, Prabhat K. Sharma, Aneta H. Worley, Umesh Lalloo, Prinita Baijnath, Anish Ambaram, Leon Naidoo, Moosa Suleman, Rajhmun Madansein, James E. McLaren, Kristin Ladell, Kelly L. MinersDavid A. Price, Samuel M. Behar, Morten Nielsen, Victoria O. Kasprowicz, Alasdair Leslie, William R. Bishai, Thumbi Ndung’u, David M. Lewinsohn

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Article number203
JournalCommunications Biology
Volume2
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Medicine (miscellaneous)

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