title: The development of colitogenic CD4(+) T cells is regulated by IL-7 in collaboration with NK cell function in a murine model of colitis.
abstract: 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.
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamaji
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagaishi
authors.forename: Teruji
authors.initials: T
authors.lastname: Totsuka
authors.forename: Michio
authors.initials: M
authors.lastname: Onizawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Suzuki
authors.forename: Naoto
authors.initials: N
authors.lastname: Tsuge
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Hasegawa
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Okamoto
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakamura
authors.forename: Hisashi
authors.initials: H
authors.lastname: Arase
authors.forename: Takanori
authors.initials: T
authors.lastname: Kanai
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D003092:Colitis / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015851:Interleukin-7 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D015851:Interleukin-7