MHC class II-expressing thymocytes suppress invariant NKT cell development.
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 alpha-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.
Li
Wei
W
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
Sofi
M Hanief
MH
Wei
Datsen G
DG
Du
Wenjun
W
Gervay-Hague
Jacquelyn
J
Renukaradhya
Gourapura J
GJ
Brutkiewicz
Randy R
RR
Chang
Cheong-Hee
CH
D000818:Animals; D002454:Cell Differentiation; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000166:cytology*; D009687:Nuclear Proteins / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics
D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators