[HTML][HTML] Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis

IJ Fuss, F Heller, M Boirivant, F Leon… - The Journal of …, 2004 - Am Soc Clin Investig
IJ Fuss, F Heller, M Boirivant, F Leon, M Yoshida, S Fichtner-Feigl, Z Yang, M Exley, A Kitani…
The Journal of clinical investigation, 2004Am Soc Clin Investig
While Crohn disease (CD) has been clearly identified as a Th1 inflammation, the
immunopathogenesis of its counterpart inflammatory bowel disease, ulcerative colitis (UC),
remains enigmatic. Here we show that lamina propria T (LPT) cells from UC patients
produce significantly greater amounts of IL-13 (and IL-5) than control cells and little IFN-γ,
whereas comparable cells from CD patients produce large amounts of IFN-γ and small
amounts of IL-13. We then show that stimulation of UC LPT cells bearing an NK marker …
While Crohn disease (CD) has been clearly identified as a Th1 inflammation, the immunopathogenesis of its counterpart inflammatory bowel disease, ulcerative colitis (UC), remains enigmatic. Here we show that lamina propria T (LPT) cells from UC patients produce significantly greater amounts of IL-13 (and IL-5) than control cells and little IFN-γ, whereas comparable cells from CD patients produce large amounts of IFN-γ and small amounts of IL-13. We then show that stimulation of UC LPT cells bearing an NK marker (CD161) with anti-CD2/anti-CD28 or with B cells expressing transfected CD1d induces substantial IL-13 production. While this provided firm evidence that the IL-13–producing cell is an NK T (NKT) cell, it became clear that this cell does not express invariant NKT cell receptors characteristic of most NKT cells since there was no increase in cells binding α-galactosylceramide–loaded tetramers, and α-galactosylceramide did not induce IL-13 secretion. Finally, we show that both human NKT cell lines as well as UC CD161+ LPT cells are cytotoxic for HT-29 epithelial cells and that this cytotoxicity is augmented by IL-13. These studies show that UC is associated with an atypical Th2 response mediated by nonclassical NKT cells producing IL-13 and having cytotoxic potential for epithelial cells.
The Journal of Clinical Investigation