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Human thymic MR1-restricted MAIT cells are innate pathogen-reactive effectors that adapt following thymic egress

2012; Elsevier BV; Volume: 6; Issue: 1 Linguagem: Inglês

10.1038/mi.2012.45

1935-3456

Marielle C. Gold, Tore Eid, Susan Smyk‐Pearson, Yvonne Eberling, Gwendolyn Swarbrick, Steven Langley, Philip R. Streeter, Deborah A. Lewinsohn, David Lewinsohn,

Immunotherapy and Immune Responses

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.