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Publication : Clonal expansion of double-positive intraepithelial lymphocytes by MHC class I-related chain A expressed in mouse small intestinal epithelium.

First Author  Park EJ Year  2003
Journal  J Immunol Volume  171
Issue  8 Pages  4131-9
PubMed ID  14530335 Mgi Jnum  J:85935
Mgi Id  MGI:2677573 Doi  10.4049/jimmunol.171.8.4131
Citation  Park EJ, et al. (2003) Clonal expansion of double-positive intraepithelial lymphocytes by MHC class I-related chain a expressed in mouse small intestinal epithelium. J Immunol 171(8):4131-9
abstractText  Expression of a distant homologue MHC class I molecule, MHC class I-related chain A (MICA), has been found to be stress inducible and limited to the intestinal epithelium. This nonclassical MHC molecule is associated with various carcinomas in humans. To understand the biological consequences of MICA expression in the gut, we generated transgenic (Tg) mice (T3(b)-MICA Tg) under the control of the T3(b) promoter. The T3(b)-MICA Tg mice expressed MICA selectively in the intestine and had an increased number of TCRalphabeta CD4CD8alphaalpha, double-positive (DP) intraepithelial lymphocytes (IELs) in the small bowel. These MICA-expanded DP IELs exhibited a bias to Vbeta8.2 and overlapped motifs of the complementarity-determining region 3 region among various Tg mice. Hence, the overexpression of MICA resulted in a clonal expansion of DP IELs. Studies in model of inflammatory bowel disease showed that transgenic MICA was able to attenuate the acute colitis induced by dextran sodium sulfate administration. Therefore, this unique in vivo model will enable investigation of possible influences of stress-inducible MICA on the gut immune surveillance.
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