Human thymic MR1-restricted MAIT cells are innate pathogen-reactive effectors that adapt following thymic egress.
Human mucosal-associated invariant T (MAIT) cells express the semi-invariant T-cell receptor (TCR) Vα7.2 and are restricted by the major histocompatibility complex-Ib molecule MR1. While MAIT cells share similarities with other innate T cells, the extent to which MAIT cells are innate and their capacity to adapt is unknown. We evaluated the function of Vα7.2(+) T cells from the thymus, cord blood, and peripheral blood. Although antigen-inexperienced MAIT cells displayed a naïve phenotype, these had intrinsic effector capacity in response to Mycobacterium tuberculosis (Mtb)-infected cells. Vα7.2(+) effector thymocytes contained signal joint TCR gene excision circles (sjTRECs) suggesting limited replication and thymic origin. In evaluating the capacity of Mtb-reactive MAIT cells to adapt, we found that those from the peripheral blood demonstrated a memory phenotype and had undergone substantial expansion, suggesting that they responded to antigenic stimulation. MAIT cells, an evolutionarily conserved T-cell subset that detects a variety of intracellular infections, share features of innate and adaptive immunity.
Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon, USA. goldm@ohsu.edu
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MC
Gold
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Eid
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Smyk-Pearson
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Eberling
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Swarbrick
S M
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Langley
P R
PR
Streeter
D A
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Lewinsohn
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Lewinsohn
D056704:Adaptive Immunity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D015778:Minor Histocompatibility Antigens; D009092:Mucous Membrane / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D060168:Thymocytes / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; C094840:MR1 protein, human; D015778:Minor Histocompatibility Antigens; D011948:Receptors, Antigen, T-Cell