A critical role of costimulation during intrathymic development of invariant NK T cells

被引:36
作者
Chung, Yeonseok [1 ]
Nurieva, Roza [1 ]
Esashi, Eiji [1 ]
Wang, Yi-Hong [1 ]
Zhou, Dapeng [2 ]
Gapin, Laurent [3 ,4 ]
Dong, Chen [1 ]
机构
[1] MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA
[2] MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA
[3] Univ Colorado, Hlth Sci Ctr, Denver, CO 80206 USA
[4] Natl Jewish Med & Res Ctr, Denver, CO 80206 USA
关键词
D O I
10.4049/jimmunol.180.4.2276
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
CD1d-restricted V alpha 14(+) invariant NK T (iNKT) cells are a specialized alpha beta 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.
引用
收藏
页码:2276 / 2283
页数:8
相关论文
共 38 条
[1]   Essential role of NKT cells producing IL-4 and IL-13 in the development of allergen-induced airway hyperreactivity [J].
Akbari, O ;
Stock, P ;
Meyer, E ;
Kronenberg, M ;
Sidobre, S ;
Nakayama, T ;
Taniguchi, M ;
Grusby, MJ ;
DeKruyff, RH ;
Umetsu, DT .
NATURE MEDICINE, 2003, 9 (05) :582-588
[2]   POSITIVE SELECTION OF MOUSE NK1(+) T-CELLS BY CD1-EXPRESSING CORTICAL THYMOCYTES [J].
BENDELAC, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (06) :2091-2096
[3]   CD1 RECOGNITION BY MOUSE NK1(+) T-LYMPHOCYTES [J].
BENDELAC, A ;
LANTZ, O ;
QUIMBY, ME ;
YEWDELL, JW ;
BENNINK, JR ;
BRUTKIEWICZ, RR .
SCIENCE, 1995, 268 (5212) :863-865
[4]   A thymic precursor to the NK T cell lineage [J].
Benlagha, K ;
Kyin, T ;
Beavis, A ;
Teyton, L ;
Bendelac, A .
SCIENCE, 2002, 296 (5567) :553-555
[5]   CD1: Antigen presentation and T cell function [J].
Brigl, M ;
Brenner, MB .
ANNUAL REVIEW OF IMMUNOLOGY, 2004, 22 :817-890
[6]   Requirement for V(alpha)14 NKT cells in IL-12-mediated rejection of tumors [J].
Cui, JQ ;
Shin, T ;
Kawano, T ;
Sato, H ;
Kondo, E ;
Toura, I ;
Kaneko, Y ;
Koseki, H ;
Kanno, M ;
Taniguchi, M .
SCIENCE, 1997, 278 (5343) :1623-1626
[7]   ICOS co-stimulatory receptor is essential for T-cell activation and function [J].
Dong, C ;
Juedes, AE ;
Temann, UA ;
Shresta, S ;
Allison, JP ;
Ruddle, NH ;
Flavell, RA .
NATURE, 2001, 409 (6816) :97-101
[8]   Restoration of NK T cell development in fyn-mutant mice by a TCR reveals a requirement for Fyn during early NK T cell ontogeny [J].
Gadue, P ;
Yin, LQ ;
Jain, S ;
Stein, PL .
JOURNAL OF IMMUNOLOGY, 2004, 172 (10) :6093-6100
[9]   NK T cell precursors exhibit differential cytokine regulation and require itk for efficient maturation [J].
Gadue, P ;
Stein, PL .
JOURNAL OF IMMUNOLOGY, 2002, 169 (05) :2397-2406
[10]   NKT cells derive from double-positive thymocytes that are positively selected by CDId [J].
Gapin, L ;
Matsuda, JL ;
Surh, CD ;
Kronenberg, M .
NATURE IMMUNOLOGY, 2001, 2 (10) :971-978