HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Chung, Y. Articles by Dong, C. PubMed PubMed Citation Articles by Chung, Y. Articles by Dong, C.

A Critical Role of Costimulation during Intrathymic Development of Invariant NK T Cells¹

Yeonseok Chung^*, Roza Nurieva^*, Eiji Esashi^*, Yi-Hong Wang^*, Dapeng Zhou, Laurent Gapin and Chen Dong^2,*

^* 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 V14⁺ 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.

This article has been cited by other articles:

				J. A. Williams, J. M. Lumsden, X. Yu, L. Feigenbaum, J. Zhang, S. M. Steinberg, and R. J. Hodes Regulation of Thymic NKT Cell Development by the B7-CD28 Costimulatory Pathway J. Immunol., July 15, 2008; 181(2): 907 - 917. [Abstract] [Full Text] [PDF]