Getting at the Guts

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Science  08 Oct 2004:
Vol. 306, Issue 5694, pp. 199
DOI: 10.1126/science.306.5694.199d

Celiac disease develops from the reaction of T cells of the small intestine to gluten present in dietary wheat, which leads ultimately to changes in villous architecture and severe impairment of mucosal function.

Studies from Hue et al. and Mersesse et al. suggest that the interaction of the immune receptor NKG2D with its ligand MICA, which is normally associated with natural killer cell and T cell activation by tumors and infectious agents, also contributes to the aberrant activity of T cells in celiac disease. Both groups observed that MICA is up-regulated on the villous epithelium of celiac patients, which Hue et al. show to depend on interleukin-15 (IL-15), a cytokine that was overexpressed in the intestinal mucosa of the patients. Both groups found that recognition of MICA by NKG2D on activated intestinal T cells from celiac patients induced killing of epithelial cells in vitro, and Mersesse et al. show that adding IL-15 also led to NKG2D-dependent acquisition of cytotoxicity by intestinal T cells from healthy individuals. Because additional IL-15 was not needed for T cell cytotoxicity in celiac patients, these results suggest that the cytokine directly primes T cell killing of villous epithelium in vivo. — SJS

Immunity 21, 367; 357 (2004).

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