Pro-inflammatory Mucosal Associated Invariant T (MAIT) cells are enriched in the airways in human tuberculosis — ASN Events
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Pro-inflammatory Mucosal Associated Invariant T (MAIT) cells are enriched in the airways in human tuberculosis (#159)

Emily B. Wong 1 2 , Marielle C Gold 3 , Umesh G. Lalloo 4 , Bongiwe Z. Xulu 1 , Zuri A. Sullivan 1 , Zoe Rogers 1 , Henrik Kloverpris 1 , Erin W. Meermeier 3 , Prabhat K. Sharma 3 , Aneta H. Worley 3 , Prinita Baijnath 5 , Anish Ambaram 5 , Leon Naidoo 5 , Rajhmun Madansein 5 , James McLaren 6 , David A. Price 6 7 , Samuel M. Behar 8 , Morten Nielsen 9 , Victoria O. Kasprowicz 1 , Alasdair Leslie 1 , Thumbi Ndung'u 1 10 , William Bishai 11 , David Lewinsohn 3
  1. KwaZulu Natal Research Institute for TB and HIV, Durban, South Africa
  2. Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, United States
  3. Oregon Health and Sciences University, Portland, OR, United States
  4. Durban University of Technology, Durban, South Africa
  5. Nelson R. Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa
  6. Cardiff University School of Medicine, Cardiff, Wales
  7. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
  8. University of Massachusetts Medical School, Worcester, Massachusetts, United States
  9. Technical University of Denmark, Lyngby, Denmark
  10. HIV Pathogenesis Programme, University of KwaZulu Natal, Durban, South Africa
  11. Johns Hopkins School of Medicine, Baltimore, Maryland, United States

Mucosal-associated invariant T (MAIT) cells are unconventional T cells that utilize semi-invariant TCRa chains to recognize bacterial, mycobacterial, and fungal riboflavin metabolites presented by MR1. MAIT cells are associated with the control of bacterial and mycobacterial infections in murine models, however their role in human tuberculosis (TB) is poorly understood.  MAIT cells are abundant in the circulation of healthy individuals but markedly diminished during active TB. It has been hypothesized, but never shown, that this is due to migration to infected tissues.  Here we report that mycobacterial-reactive MAIT cells with pro-inflammatory effector function are present in healthy lungs and highly enriched in the bronchoalveolar (BAL) fluid of people with pulmonary TB. T cell receptor (TCR) repertoire analysis reveals clonal MAIT cell expansions in the BAL and the lung granulomas of subjects with TB. Furthermore, while MAIT cells with canonical TCRs are highly shared between donors, MAIT cells with donor-unique TCRs are often dominant. The high level of enrichment of MAIT cells with pro-inflammatory effector function in the airways of TB-infected individuals highlights a potential and previously unrecognized role for this class of lymphocytes in the pulmonary immune response to Mtb in humans.