A Y Chromosome-Linked Factor Impairs NK T Development

Abstract

Vα14 invariant (Vα14i) NK T cell development is unique from mainstream T cell selection, and the polygenic factors that influence NK T cell ontogeny are still unclear. In this study, we report the absence of Vα14i NK T cells in B6.IFN-αβR1−/− male mice, whereas both the conventional T and NK cell populations are relatively unaffected. The lack of Vα14i NK T cells in the B6.IFN-αβR1−/− males is not due to an insufficient level of CD1d1 or a defect in CD1d1-Ag presentation, but it is intrinsic to the male Vα14i NK T cells. This surprising defect displays ≥99% penetrance in the male population, whereas female mice remain unaffected, indicating the deficiency is not X linked. Analysis of the Vα14i NK T cell compartment in B6.Tyk2−/−, B6.STAT1−/−, 129.IFN-αβR1−/−, and B6.IFN-αβR1−/+ mice demonstrate that the deficiency is linked to the Y chromosome, but independent of IFN-αβ. This is the first study demonstrating that Y-linked genes can exclusively impact Vα14i NK T development and further highlight the unique ontogeny of these innate T cells.