The development of colitogenic CD4 ⁺ T cells is regulated by IL-7 in collaboration with NK cell function in a murine model of colitis

We previously reported that IL-7 ^-/-RAG ^-/- mice receiving naive T cells failed to induce colitis. Such abrogation of colitis may be associated with not only incomplete T cell maintenance due to the lack of IL-7, but also with the induction of colitogenic CD4 ⁺ T cell apoptosis at an early stage of colitis development. Moreover, NK cells may be associated with the suppression of pathogenic T cells in vivo, and they may induce apoptosis of CD4 ⁺ T cells. To further investigate these roles of NK cells, RAG ^-/- and IL-7 ^-/-RAG ^-/-mice that had received naive T cells were depleted of NK cells using anti-asialo GM1 and anti-NK1.1 Abs. NK cell depletion at an early stage, but not at a later stage during colitogenic effector memory T cell (T _EM) development, resulted in exacerbated colitis in recipient mice even in the absence of IL-7. Increased CD44 ⁺CD62L ^- T _EM and unique CD44 ^-CD62L ^- T cell subsets were observed in the T cell-reconstituted RAG ^-/- recipients when NK cells were depleted, although Fas, DR5, and IL-7R expressions in this subset differed from those in the CD44 ⁺CD62L ^- T _EM subset. NK cell characteristics were the same in the presence or absence of IL-7 in vitro and in vivo. These results suggest that NK cells suppress colitis severity in T cell-reconstituted RAG ^-/- and IL-7 ^-/-RAG ^-/- recipient mice through targeting of colitogenic CD4 ⁺CD44 ⁺CD62L ^- T _EM and, possibly, of the newly observed CD4 ⁺CD44 ^-CD62L ^- subset present at the early stage of T cell development.