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-17 CD161(++)CD8 alpha beta(+) T cells exist in cord blood, from which a prominent MAIT cell (TCR V alpha 7.2(+)) population emerges postnatally. During this expansion, CD8 alpha alpha T cells appear exclusively within a CD161(++)CD8(+)/MAIT subset, sharing cytokine production, chemokine-receptor expression, TCR-usage, and transcriptional profiles with their CD161(++)CD8 alpha beta(+) 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 CD8 alpha alpha cells in man. (Blood. 2012;119(2):422-433)