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

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556 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)834-842
Number of pages9
JournalJournal of Immunology
Issue number2
Publication statusPublished - Jan 15 2004

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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