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++CD8αβ+ T cells exist in cord blood, from which a prominent MAIT cell (TCR Vα7.2+) population emerges post-natally. During this expansion, CD8αα T cells appear exclusively within a CD161++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.