Repeated alpha-galactosylceramide administration results in expansion of NK T cells and alleviates inflammatory dermatitis in MRL-lpr/lpr mice.
NK T (NKT) cells expressing the invariant Valpha14-Jalpha18 TCR alpha-chain recognize glycolipid Ags such as alpha-galactosylceramide (alpha-GalCer) presented by the MHC class I-like molecule CD1d. Upon activation by alpha-GalCer, invariant NKT cells secrete multiple cytokines and confer protection in certain immune-mediated disorders. Here we have investigated the role of NKT cells in the development of inflammatory dermatitis in MRL-lpr/lpr mice, which shares features with lupus in humans. Our results show that the numbers Sand functions of NKT (TCRbeta(+)CD1d/alpha-GalCer tetramer(+)) cells, particularly of the NK1.1(-) subset, are reduced in MRL-lpr/lpr mice compared with MRL-fas/fas and/or nonautoimmune C3H/Hej and BALB/c mice. Repeated treatments with alpha-GalCer result in the expansion of NKT cells and alleviate dermatitis in MRL-lpr/lpr mice. Our results indicate that NKT cell deficiency can be corrected by repeated alpha-GalCer treatment and that NKT cells may play a protective role in inflammatory dermatitis of lupus-prone mice.
Yang
Jun-Qi
JQ
Autoimmunity and Tolerance Laboratory, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
Saxena
Vijay
V
Xu
Honglin
H
Van Kaer
Luc
L
Wang
Chyung-Ru
CR
Singh
Ram Raj
RR
D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D003872:Dermatitis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D004334:Drug Administration Schedule; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D007274:Injections, Intraperitoneal; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology* / Q000473:pathology; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D019463:Mice, Inbred MRL lpr; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000473:pathology
D005699:Galactosylceramides