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* Department of Immunology and
Department of Melanoma Medical Oncology, M. D. Anderson Cancer Center, Houston, TX 77030; and
University of Colorado Health Science Center and National Jewish Medical and Research Center, Denver, CO 80206
CD1d-restricted V
14+ invariant NK T (iNKT) cells are a specialized β 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This study was funded in part by grants from the National Institutes of Health (AI50746 to C.D. and AI057485 to L.G.). R.N. receives a postdoctoral fellowship from Arthritis Foundation and a Scientist Development Grant from American Heart Association. D.Z. is funded by M. D. Anderson Cancer Center and by a Developmental Award of Joe Moakley Leukemia Specialized Program of Research Excellence grant from National Cancer Institute. C.D. is a Cancer Research Institute Investigator and a Trust Fellow of M. D. Anderson Cancer Center.
2 Address correspondence and reprint requests to Dr. Chen Dong, M. D. Anderson Cancer Center, 7455 Fannin, Unit 906, Houston, TX 77030. E-mail address: cdong{at}mdanderson.org
3 Abbreviations used in this paper: iNKT, invariant NK T cells; GC, -galactosylceramide; WT, wild type; BM, bone marrow.
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