A ROLE FOR NK CELLS AS REGULATORS OF CD4(-CELLS IN A TRANSFER MODEL OF COLITIS() T)

Previous studies have shown that the chronic inflammation observed in the colon of IL-10-deficient (IL-10(-/-)) mice is mediated by CD4(+) T h1 T cells and is dependent on the presence of IFN-gamma for its initi al development, As CD4(+) T cells from IL-10(-/-) mice will cause coli tis when transferred into recombinase-activating gene (Rag)-deficient recipients, we considered the possibility that the recipients' NK cell s could be an important source of IFN-gamma for the development of col itis. Therefore, the ability of IL-10(-/-)CD4(+) T cells to cause coli tis in Rag-deficient recipients that had been depleted of Mt cells was tested, Contrary to our expectations, NK cell-depleted recipients of IL-10(-/-) CD4(+) T cells developed accelerated disease compared with nondepleted recipients. Furthermore, CD4(+) T cells from normal mice ( IL-10(+/+)) also caused colitis in NK cell-depleted recipient mice, bu t not in nondepleted recipients. NK cells inhibited effector CD4(+)CD4 5RB(high) T cells, and subsequent experiments showed that this effect was dependent on perforin, Thus NK cells can play an important role in down-regulating Th1-mediated colitis by controlling the responses of effector T cells to gut bacteria.