Human MAIT and CD8αα cells develop from a pool of type-17 precommitted CD8⁺ T cells

Human mucosal associated invariant T (MAIT) CD8+ and Tc17 cells are important tissue-homing cell populations, characterized by high expression of CD161 (++) and type-17 differentiation, but their origins and relationships remain poorly defined. By transcriptional and functional analyses, we demonstrate that a pool of polyclonal, precommitted type-17CD161 ++CD8αβ+ T cells exist in cord blood, from which a prominent MAIT cell(TCR Vα7.2+) population emerges postnatally. During this expansion, CD8αα T cells appear exclusively within aCD161++CD8+/MAIT subset, sharing cytokine production, chemokine-receptor expression, TCR-usage, and transcriptional profiles with their CD161++CD8αβ+ counterparts. Our data demonstrate the origin and differentiation pathway of MAIT-cells from a naive type-17 precommitted CD161++CD8+T-cell pool and the distinct phenotype and function of CD8αα cells in man. © 2012 by The American Society of Hematology.