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-Galactosylceramide Administration Results in Expansion of NK T Cells and Alleviates Inflammatory Dermatitis in MRL-lpr/lpr Mice 1
* Autoimmunity and Tolerance Laboratory, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45267;
Gwen Knapp Center, University of Chicago, Chicago, IL 60637; and
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
NK T (NKT) cells expressing the invariant V
14-J18 TCR -chain recognize glycolipid Ags such as -galactosylceramide (-GalCer) presented by the MHC class I-like molecule CD1d. Upon activation by -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 (TCR
+CD1d/-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 -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 -GalCer treatment and that NKT cells may play a protective role in inflammatory dermatitis of lupus-prone mice.
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