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

• Published in: The Journal of immunology (1950) Vol. 188; no. 6; pp. 2524 - 2536
• Main Authors: Yamaji, Osamu, Nagaishi, Takashi, Totsuka, Teruji, Onizawa, Michio, Suzuki, Masahiro, Tsuge, Naoto, Hasegawa, Atsuhiko, Okamoto, Ryuichi, Tsuchiya, Kiichiro, Nakamura, Tetsuya, Arase, Hisashi, Kanai, Takanori, Watanabe, Mamoru
• Format: Journal Article
• Language: English
• Published: United States 15.03.2012
• Subjects: Animals; CD4-Positive T-Lymphocytes - immunology; Cell Separation; Colitis - immunology; Colitis - pathology; Disease Models, Animal; Flow Cytometry; Interleukin-7 - immunology; Killer Cells, Natural - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; T-Lymphocyte Subsets - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1100371

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.