A role for NK cells as regulators of CD4+ T cells in a transfer model of colitis

Previous studies have shown that the chronic inflammation observed in the colon of IL-10-deficient (IL-10(-/-)) mice is mediated by CD4(+) Th1 T cells and is dependent on the presence of IFN-gamma for its initial development, As CD4(+) T cells from IL-10(-/-) mice will cause colitis when transferred into recombinase-activating gene (Rag)-deficient recipients, we considered the possibility that the recipients' NK cells could be an important source of IFN-gamma for the development of colitis. Therefore, the ability of IL-10(-/-)CD4(+) T cells to cause colitis 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, but not in nondepleted recipients. NK cells inhibited effector CD4(+)CD45RB(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.