A critical role of costimulation during intrathymic development of invariant NK T cells.
CD1d-restricted Valpha14(+) invariant NK T (iNKT) cells are a specialized alphabeta T cell subset that regulates both innate and adaptive immunity. Although costimulatory molecules are required for the activation of conventional T cells and for the development of Foxp3(+) T cells, their role in iNKT cell regulation is unclear. Here we report that mice deficient in CD80/CD86 and/or B7h exhibit severe defects in thymic iNKT cell maturation, associated with largely reduced iNKT cell number in the thymus and the periphery. We show that costimulation is necessary for the optimal expansion of postselected NK1.1(-) immature iNKT cells in the thymus and for the proper expression of the maturation markers T-bet and CD122. Surprisingly, costimulatory molecules on both hemopoietic and nonhematopoietic cells are required for iNKT cell development. Our results thus demonstrate a previously unknown function of costimulation in the intrathymic development of iNKT cells, distinct from that of conventional T cells and regulatory T cells.
Chung
Yeonseok
Y
Department of Immunology, M.D. Anderson Cancer Center, 7455 Fannin, Houston, TX 77030, USA.
Nurieva
Roza
R
Esashi
Eiji
E
Wang
Yi-Hong
YH
Zhou
Dapeng
D
Gapin
Laurent
L
Dong
Chen
C
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation