Long-lived colitogenic CD4+ memory T cells residing outside the intestine participate in the perpetuation of chronic colitis

Yasuhiro Nemoto, Takanori Kanai, Kaori Kameyama, Tamako Shinohara, Naoya Sakamoto, Teruji Totsuka, Ryuichi Okamoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Tetsuo Sudo, Satoshi Matsumoto, Mamoru Watanabe

研究成果: Article

24 引用 (Scopus)

抄録

To understand the perpetuation of inflammatory bowel disease (IBD), it is important to clarify whether the colitogenic CD4+ T cells are self-limited effector or long-lived memory T cells. We here investigate the latency of colitogenic CD4+ T cells in the remission stage of colitis under germfree (GF) conditions. We isolated splenic (SP) CD4+ T cells from colitic CD4+CD45RBhigh T cell-injected SCID mice maintained under specific pathogen-free (SPF) conditions and transferred them into SPF or GF SCID mice. Donor colitic SP CD4+ T cells have a characteristic CD44highCD62L-IL-7Rαhigh effector-memory T-type phenotype. Six weeks after transfer of cells to GF SCID mice, one group of mice was continued in GF conditions (GF→GF), and the other was transferred into SPF conditions (GF→SPF). GF→SPF but not GF→GF SCID mice developed colitis with elevated production of Th1 and Th17 cytokines at 4 wk after transfer. Surprisingly, a large number of CD4 + effector-memory T cells and a small but substantial number of central-memory T cells remained resident in SP and bone marrow, but not in lamina propria, of the GF→GF SCID recipients. Consistent with this, GF3SPF but not GF→GF SCID mice rapidly developed colitis. Taken together, these findings suggest that long-lived colitogenic memory CD4+ cells can be established even in the presence of commensal Ags, reside outside the intestine in the absence of commensal bacteria, and participate in the perpetuation of colitis. Thus, blocking a stimulus of colitogenic memory CD4+ cells such as IL-7 may have therapeutic benefit for treatment of inflammatory bowel disease.

元の言語English
ページ(範囲)5059-5068
ページ数10
ジャーナルJournal of Immunology
183
発行部数8
DOI
出版物ステータスPublished - 2009 10 15
外部発表Yes

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Colitis
Intestines
SCID Mice
T-Lymphocytes
Specific Pathogen-Free Organisms
Inflammatory Bowel Diseases
Interleukin-7
Mucous Membrane
Bone Marrow
Cytokines
Bacteria
Phenotype

ASJC Scopus subject areas

  • Immunology

これを引用

Long-lived colitogenic CD4+ memory T cells residing outside the intestine participate in the perpetuation of chronic colitis. / Nemoto, Yasuhiro; Kanai, Takanori; Kameyama, Kaori; Shinohara, Tamako; Sakamoto, Naoya; Totsuka, Teruji; Okamoto, Ryuichi; Tsuchiya, Kiichiro; Nakamura, Tetsuya; Sudo, Tetsuo; Matsumoto, Satoshi; Watanabe, Mamoru.

:: Journal of Immunology, 巻 183, 番号 8, 15.10.2009, p. 5059-5068.

研究成果: Article

Nemoto, Y, Kanai, T, Kameyama, K, Shinohara, T, Sakamoto, N, Totsuka, T, Okamoto, R, Tsuchiya, K, Nakamura, T, Sudo, T, Matsumoto, S & Watanabe, M 2009, 'Long-lived colitogenic CD4+ memory T cells residing outside the intestine participate in the perpetuation of chronic colitis', Journal of Immunology, 巻. 183, 番号 8, pp. 5059-5068. https://doi.org/10.4049/jimmunol.0803684
Nemoto, Yasuhiro ; Kanai, Takanori ; Kameyama, Kaori ; Shinohara, Tamako ; Sakamoto, Naoya ; Totsuka, Teruji ; Okamoto, Ryuichi ; Tsuchiya, Kiichiro ; Nakamura, Tetsuya ; Sudo, Tetsuo ; Matsumoto, Satoshi ; Watanabe, Mamoru. / Long-lived colitogenic CD4+ memory T cells residing outside the intestine participate in the perpetuation of chronic colitis. :: Journal of Immunology. 2009 ; 巻 183, 番号 8. pp. 5059-5068.
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abstract = "To understand the perpetuation of inflammatory bowel disease (IBD), it is important to clarify whether the colitogenic CD4+ T cells are self-limited effector or long-lived memory T cells. We here investigate the latency of colitogenic CD4+ T cells in the remission stage of colitis under germfree (GF) conditions. We isolated splenic (SP) CD4+ T cells from colitic CD4+CD45RBhigh T cell-injected SCID mice maintained under specific pathogen-free (SPF) conditions and transferred them into SPF or GF SCID mice. Donor colitic SP CD4+ T cells have a characteristic CD44highCD62L-IL-7Rαhigh effector-memory T-type phenotype. Six weeks after transfer of cells to GF SCID mice, one group of mice was continued in GF conditions (GF→GF), and the other was transferred into SPF conditions (GF→SPF). GF→SPF but not GF→GF SCID mice developed colitis with elevated production of Th1 and Th17 cytokines at 4 wk after transfer. Surprisingly, a large number of CD4 + effector-memory T cells and a small but substantial number of central-memory T cells remained resident in SP and bone marrow, but not in lamina propria, of the GF→GF SCID recipients. Consistent with this, GF3SPF but not GF→GF SCID mice rapidly developed colitis. Taken together, these findings suggest that long-lived colitogenic memory CD4+ cells can be established even in the presence of commensal Ags, reside outside the intestine in the absence of commensal bacteria, and participate in the perpetuation of colitis. Thus, blocking a stimulus of colitogenic memory CD4+ cells such as IL-7 may have therapeutic benefit for treatment of inflammatory bowel disease.",
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T1 - Long-lived colitogenic CD4+ memory T cells residing outside the intestine participate in the perpetuation of chronic colitis

AU - Nemoto, Yasuhiro

AU - Kanai, Takanori

AU - Kameyama, Kaori

AU - Shinohara, Tamako

AU - Sakamoto, Naoya

AU - Totsuka, Teruji

AU - Okamoto, Ryuichi

AU - Tsuchiya, Kiichiro

AU - Nakamura, Tetsuya

AU - Sudo, Tetsuo

AU - Matsumoto, Satoshi

AU - Watanabe, Mamoru

PY - 2009/10/15

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AB - To understand the perpetuation of inflammatory bowel disease (IBD), it is important to clarify whether the colitogenic CD4+ T cells are self-limited effector or long-lived memory T cells. We here investigate the latency of colitogenic CD4+ T cells in the remission stage of colitis under germfree (GF) conditions. We isolated splenic (SP) CD4+ T cells from colitic CD4+CD45RBhigh T cell-injected SCID mice maintained under specific pathogen-free (SPF) conditions and transferred them into SPF or GF SCID mice. Donor colitic SP CD4+ T cells have a characteristic CD44highCD62L-IL-7Rαhigh effector-memory T-type phenotype. Six weeks after transfer of cells to GF SCID mice, one group of mice was continued in GF conditions (GF→GF), and the other was transferred into SPF conditions (GF→SPF). GF→SPF but not GF→GF SCID mice developed colitis with elevated production of Th1 and Th17 cytokines at 4 wk after transfer. Surprisingly, a large number of CD4 + effector-memory T cells and a small but substantial number of central-memory T cells remained resident in SP and bone marrow, but not in lamina propria, of the GF→GF SCID recipients. Consistent with this, GF3SPF but not GF→GF SCID mice rapidly developed colitis. Taken together, these findings suggest that long-lived colitogenic memory CD4+ cells can be established even in the presence of commensal Ags, reside outside the intestine in the absence of commensal bacteria, and participate in the perpetuation of colitis. Thus, blocking a stimulus of colitogenic memory CD4+ cells such as IL-7 may have therapeutic benefit for treatment of inflammatory bowel disease.

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