Human MAIT and CD8αα cells develop from a pool of type-17 precommitted CD8+ T cells.
Walker LJ., Kang YH., Smith MO., Tharmalingham H., Ramamurthy N., Fleming VM., Sahgal N., Leslie A., Oo Y., Geremia A., Scriba TJ., Hanekom WA., Lauer GM., Lantz O., Adams DH., Powrie F., Barnes E., Klenerman P.
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.