TGF-β1 Plays an Important Role in the Mechanism of CD4 +CD25+ Regulatory T Cell Activity in Both Humans and Mice

Kazuhiko Nakamura, Atsushi Kitani, Ivan Fuss, Aasta Pedersen, Naohiko Harada, Hajime Nawata, Warren Strober

研究成果: ジャーナルへの寄稿記事

523 引用 (Scopus)

抄録

In previous studies, we have shown that murine CD4+CD25 + regulatory T cells produce high levels of TGF-β1 in a cell surface and/or secreted form, and blockade of such TGF-β1 by anti-TGF-β curtails the ability of these cells to suppress CD25 - T cell proliferation and B cell Ig production in in vitro suppressor assays. In further support for the role of TGF-β1 in suppression by CD4+CD25+ T cells, we show in this study that another TGF-β1-blocking molecule, recombinant latency-associated peptide of TGF-β1 (rLAP), also reverses suppression by mouse CD4 +CD25+ T cells as well as their human counterparts, CD4+CD25high T cells. In addition, we show that CD25 - T cells exposed to CD4+CD25+ T cells in vitro manifest activation of Smad-2 and induction of CD103, the latter a TGF-β-inducible surface integrin. In further studies, we show that while CD4+CD25+ T cells from TGF-β1-deficient mice can suppress CD25- T cell proliferation in vitro, these cells do not protect recipient mice from colitis in the SCID transfer model in vivo, and, in addition, CD4+LAP+, but not CD4+LAP - T cells from normal mice protect recipient mice from colitis in this model. Together, these studies demonstrate that TGF-β1 produced by CD4+CD25+ T cells is involved in the suppressor activity of these cells, particularly in their ability to regulate intestinal inflammation.

元の言語英語
ページ(範囲)834-842
ページ数9
ジャーナルJournal of Immunology
172
発行部数2
出版物ステータス出版済み - 1 15 2004

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Regulatory T-Lymphocytes
T-Lymphocytes
Colitis
Cell Proliferation
Integrins
B-Lymphocytes
Inflammation
Peptides

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

これを引用

Nakamura, K., Kitani, A., Fuss, I., Pedersen, A., Harada, N., Nawata, H., & Strober, W. (2004). TGF-β1 Plays an Important Role in the Mechanism of CD4 +CD25+ Regulatory T Cell Activity in Both Humans and Mice. Journal of Immunology, 172(2), 834-842.

TGF-β1 Plays an Important Role in the Mechanism of CD4 +CD25+ Regulatory T Cell Activity in Both Humans and Mice. / Nakamura, Kazuhiko; Kitani, Atsushi; Fuss, Ivan; Pedersen, Aasta; Harada, Naohiko; Nawata, Hajime; Strober, Warren.

:: Journal of Immunology, 巻 172, 番号 2, 15.01.2004, p. 834-842.

研究成果: ジャーナルへの寄稿記事

Nakamura, K, Kitani, A, Fuss, I, Pedersen, A, Harada, N, Nawata, H & Strober, W 2004, 'TGF-β1 Plays an Important Role in the Mechanism of CD4 +CD25+ Regulatory T Cell Activity in Both Humans and Mice', Journal of Immunology, 巻. 172, 番号 2, pp. 834-842.
Nakamura K, Kitani A, Fuss I, Pedersen A, Harada N, Nawata H その他. TGF-β1 Plays an Important Role in the Mechanism of CD4 +CD25+ Regulatory T Cell Activity in Both Humans and Mice. Journal of Immunology. 2004 1 15;172(2):834-842.
Nakamura, Kazuhiko ; Kitani, Atsushi ; Fuss, Ivan ; Pedersen, Aasta ; Harada, Naohiko ; Nawata, Hajime ; Strober, Warren. / TGF-β1 Plays an Important Role in the Mechanism of CD4 +CD25+ Regulatory T Cell Activity in Both Humans and Mice. :: Journal of Immunology. 2004 ; 巻 172, 番号 2. pp. 834-842.
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abstract = "In previous studies, we have shown that murine CD4+CD25 + regulatory T cells produce high levels of TGF-β1 in a cell surface and/or secreted form, and blockade of such TGF-β1 by anti-TGF-β curtails the ability of these cells to suppress CD25 - T cell proliferation and B cell Ig production in in vitro suppressor assays. In further support for the role of TGF-β1 in suppression by CD4+CD25+ T cells, we show in this study that another TGF-β1-blocking molecule, recombinant latency-associated peptide of TGF-β1 (rLAP), also reverses suppression by mouse CD4 +CD25+ T cells as well as their human counterparts, CD4+CD25high T cells. In addition, we show that CD25 - T cells exposed to CD4+CD25+ T cells in vitro manifest activation of Smad-2 and induction of CD103, the latter a TGF-β-inducible surface integrin. In further studies, we show that while CD4+CD25+ T cells from TGF-β1-deficient mice can suppress CD25- T cell proliferation in vitro, these cells do not protect recipient mice from colitis in the SCID transfer model in vivo, and, in addition, CD4+LAP+, but not CD4+LAP - T cells from normal mice protect recipient mice from colitis in this model. Together, these studies demonstrate that TGF-β1 produced by CD4+CD25+ T cells is involved in the suppressor activity of these cells, particularly in their ability to regulate intestinal inflammation.",
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AU - Strober, Warren

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