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

Osamu Yamaji, Takashi Nagaishi, Teruji Totsuka, Michio Onizawa, Masahiro Suzuki, Naoto Tsuge, Atsuhiko Hasegawa, Ryuichi Okamoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Hisashi Arase, Takanori Kanai, Mamoru Watanabe

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2524-2536
Number of pages13
JournalJournal of Immunology
Volume188
Issue number6
DOIs
Publication statusPublished - 2012 Mar 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'The development of colitogenic CD4 <sup>+</sup> T cells is regulated by IL-7 in collaboration with NK cell function in a murine model of colitis'. Together they form a unique fingerprint.

  • Cite this

    Yamaji, O., Nagaishi, T., Totsuka, T., Onizawa, M., Suzuki, M., Tsuge, N., Hasegawa, A., Okamoto, R., Tsuchiya, K., Nakamura, T., Arase, H., Kanai, T., & Watanabe, M. (2012). The development of colitogenic CD4 + T cells is regulated by IL-7 in collaboration with NK cell function in a murine model of colitis. Journal of Immunology, 188(6), 2524-2536. https://doi.org/10.4049/jimmunol.1100371