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

Emily B. Wong; Marielle C. 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. Miners; David A. Price; Samuel M. Behar; Morten Nielsen; Victoria O. Kasprowicz; Alasdair Leslie; William R. Bishai; Thumbi Ndung’u; David M. Lewinsohn

doi:10.1038/s42003-019-0442-2

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

Emily B. Wong, Marielle C. 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^*

^*Corresponding author for this work

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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 language	English
Article number	203
Journal	Communications Biology
Volume	2
Issue number	1
Number of pages	13
DOIs	https://doi.org/10.1038/s42003-019-0442-2
Publication status	Published - 2019

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Wong, E. B., Gold, M. C., Meermeier, E. W., Xulu, B. Z., Khuzwayo, S., Sullivan, Z. A., Mahyari, E., Rogers, Z., Kløverpris, H., Sharma, P. K., Worley, A. H., Lalloo, U., Baijnath, P., Ambaram, A., Naidoo, L., Suleman, M., Madansein, R., McLaren, J. E., Ladell, K., ... Lewinsohn, D. M. (2019). TRAV1-2⁺ CD8⁺ T-cells including oligoconal expansions of MAIT cells are enriched in the airways in human tuberculosis. Communications Biology, 2(1), [203]. https://doi.org/10.1038/s42003-019-0442-2

Wong, EB, Gold, MC, Meermeier, EW, Xulu, BZ, Khuzwayo, S, Sullivan, ZA, Mahyari, E, Rogers, Z, Kløverpris, H, Sharma, PK, Worley, AH, Lalloo, U, Baijnath, P, Ambaram, A, Naidoo, L, Suleman, M, Madansein, R, McLaren, JE, Ladell, K, Miners, KL, Price, DA, Behar, SM, Nielsen, M, Kasprowicz, VO, Leslie, A, Bishai, WR, Ndung’u, T & Lewinsohn, DM 2019, 'TRAV1-2⁺ CD8⁺ T-cells including oligoconal expansions of MAIT cells are enriched in the airways in human tuberculosis', Communications Biology, vol. 2, no. 1, 203. https://doi.org/10.1038/s42003-019-0442-2

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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.}",

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AU - Gold, Marielle C.

AU - Meermeier, Erin W.

AU - Xulu, Bongiwe Z.

AU - Khuzwayo, Sharon

AU - Sullivan, Zuri A.

AU - Mahyari, Eisa

AU - Rogers, Zoe

AU - Kløverpris, Hénrik

AU - Sharma, Prabhat K.

AU - Worley, Aneta H.

AU - Lalloo, Umesh

AU - Baijnath, Prinita

AU - Ambaram, Anish

AU - Naidoo, Leon

AU - Suleman, Moosa

AU - Madansein, Rajhmun

AU - McLaren, James E.

AU - Ladell, Kristin

AU - Miners, Kelly L.

AU - Price, David A.

AU - Behar, Samuel M.

AU - Nielsen, Morten

AU - Kasprowicz, Victoria O.

AU - Leslie, Alasdair

AU - Bishai, William R.

AU - Ndung’u, Thumbi

AU - Lewinsohn, David M.

PY - 2019

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N2 - 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.

AB - 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.

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