Dataset Information

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 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.

SUBMITTER: Wong EB

PROVIDER: S-EPMC6549148 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Wong Emily B EB Gold Marielle C MC Meermeier Erin W EW Xulu Bongiwe Z BZ Khuzwayo Sharon S Sullivan Zuri A ZA Mahyari Eisa E Rogers Zoe Z Kløverpris Hénrik H Sharma Prabhat K PK Worley Aneta H AH Lalloo Umesh U Baijnath Prinita P Ambaram Anish A Naidoo Leon L Suleman Moosa M Madansein Rajhmun R McLaren James E JE Ladell Kristin K Miners Kelly L KL Price David A DA Behar Samuel M SM Nielsen Morten M Kasprowicz Victoria O VO Leslie Alasdair A Bishai William R WR Ndung'u Thumbi T Lewinsohn David M DM

Communications biology 20190605

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 bronch ...[more]

PMID: 31231693

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Project description:Background & aimsCD161-expressing CD8+ T cells consist of mucosal-associated invariant T cells with semi-invariant T-cell receptor (TCR) use and non-mucosal-associated invariant T CD161+CD8+ T cells with polyclonal TCR repertoire. Although CD161+CD8+ T cells are enriched in liver and embrace hepatitis B virus (HBV)-specific T cells in chronic hepatitis B (CHB) patients, their roles in disease progression remain poorly understood. This study aimed to decipher their profiling and dynamic changes during chronic HBV infection.MethodsBlood samples from 257 CHB patients and nontumor liver specimens from 73 HBV-positive patients were analyzed for CD161+CD8+ T-cell characterization by flow cytometry, TCR repertoire determination, transcriptomic analyses, and cell experiments.ResultsCD161+CD8+ T cells were increased and hyperactivated in patients, while positive correlation between the CD161+CD8+ T-cell ratio and HBV-DNA level suggested this was insufficient to control HBV replication. The overlap of complementarity determining region 3 sequences supported the switch between CD161-CD8+ and CD161+CD8+ populations. Although CD161+CD8+ T cells were endowed with innateness phenotype and enhanced antiviral capacity, the population from patients had impaired type I cytokine production, and increased interleukin 17 and granzyme B secretion. The increased CD161+CD8+ T cells and their increased granzyme B secretion correlated positively with inflammation-associated liver injury. Hepatic CD161+CD8+ T cells showed neutrophil-related pathogenic potential because they had increased transcript signatures and proinflammatory cytokine production in neutrophil recruitment- and response-related pathways that changed consistently in the injured liver.ConclusionsOur results highlight the reduced antiviral potency but increased pathogenic potential of CD161+CD8+ T cells in CHB patients, supporting CD161 expression as a marker of pathogenic CD8+ T subset and the intervention target for liver injury.

Dataset Information

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

Publications

TRAV1-2<sup>+</sup> CD8<sup>+</sup> T-cells including oligoconal expansions of MAIT cells are enriched in the airways in human tuberculosis.

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