1. ¹Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA
2. ²Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, MI, USA
3. ³Committee on Immunology, University of Chicago, Chicago, IL, USA
4. ⁴Department of Chemistry, University of California Davis, Davis, CA, USA
5. ⁵Department of Microbiology and Immunology, Indiana University School of Medicine, The Walther Cancer Institute, Indianapolis, IN, USA

Correspondence: Dr C-H Chang, Department of Microbiology and Immunology, The University of Michigan Medical School, 5641 Medical Science Bldg II, Ann Arbor, MI 48109-0620, USA. E-mail: heechang@umich.edu

⁶These authors contributed equally to this work.

Received 28 July 2008; Revised 29 September 2008; Accepted 1 October 2008; Published online 4 November 2008.

Abstract

Natural killer T (NKT) cells are positively selected on cortical thymocytes expressing the non-classical major histocompatibility complex (MHC) class I CD1d molecules. However, it is less clear how NKT cells are negatively selected in the thymus. In this study, we investigated the role of MHC class II expression in NKT cell development. Transgenic mice expressing MHC class II on thymocytes and peripheral T cells had a marked reduction in invariant NKT (iNKT) cells. Reduced numbers of iNKT cells correlated with the absence of in vivo production of cytokines in response to the iNKT cell agonist -galactosylceramide. Using mixed bone marrow chimeras, we found that MHC class II-expressing thymocytes suppressed the development of iNKT cells in trans in a CD4-dependent manner. Our observations have significant implications for human iNKT cell development as human thymocytes express MHC class II, which can lead to an inefficient selection of iNKT cells.