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

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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

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Interleukin-7
Colitis
Natural Killer Cells
T-Lymphocytes
Apoptosis
T-Lymphocyte Subsets
Maintenance

ASJC Scopus subject areas

  • Immunology

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

In: Journal of Immunology, Vol. 188, No. 6, 15.03.2012, p. 2524-2536.

Research output: Contribution to journalArticle

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, vol. 188, no. 6, pp. 2524-2536. https://doi.org/10.4049/jimmunol.1100371
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. / The development of colitogenic CD4 + T cells is regulated by IL-7 in collaboration with NK cell function in a murine model of colitis. In: Journal of Immunology. 2012 ; Vol. 188, No. 6. pp. 2524-2536.
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AU - Nagaishi, Takashi

AU - Totsuka, Teruji

AU - Onizawa, Michio

AU - Suzuki, Masahiro

AU - Tsuge, Naoto

AU - Hasegawa, Atsuhiko

AU - Okamoto, Ryuichi

AU - Tsuchiya, Kiichiro

AU - Nakamura, Tetsuya

AU - Arase, Hisashi

AU - Kanai, Takanori

AU - Watanabe, Mamoru

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N2 - 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.

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