A Y chromosome-linked factor impairs NK T development.
Valpha14 invariant (Valpha14i) 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 Valpha14i NK T cells in B6.IFN-alphabetaR1-/- male mice, whereas both the conventional T and NK cell populations are relatively unaffected. The lack of Valpha14i NK T cells in the B6.IFN-alphabetaR1-/- males is not due to an insufficient level of CD1d1 or a defect in CD1d1-Ag presentation, but it is intrinsic to the male Valpha14i NK T cells. This surprising defect displays >or=99% penetrance in the male population, whereas female mice remain unaffected, indicating the deficiency is not X linked. Analysis of the Valpha14i NK T cell compartment in B6.Tyk2-/-, B6.STAT1-/-, 129.IFN-alphabetaR1-/-, and B6.IFN-alphabetaR1-/+ mice demonstrate that the deficiency is linked to the Y chromosome, but independent of IFN-alphabeta. This is the first study demonstrating that Y-linked genes can exclusively impact Valpha14i NK T development and further highlight the unique ontogeny of these innate T cells.
Wesley
Johnna D
JD
Department of Molecular Microbiology and Immunolog, Division of Biology and Medicine, Brown University, Providence, RI 02912, USA.
Tessmer
Marlowe S
MS
Paget
Christophe
C
Trottein
François
F
Brossay
Laurent
L
D000818:Animals; D018949:Antigens, CD1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D055610:Antigens, CD1d; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology*; D003433:Crosses, Genetic; D005260:Female; D008040:Genetic Linkage; D006131:Growth Inhibitors / Q000235:genetics*; D007370:Interferon Type I / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000235:genetics; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014998:Y Chromosome / Q000235:genetics*