CD4+CD25+ Regulatory T Cells Can Mediate Suppressor Function in the Absence of Transforming Growth Factor β1 Production and Responsiveness
By C. Piccirillo, J. Letterio, A. Thornton, R. McHugh, M. Mamura, H. Mizuhara, E. Shevach. Journal of Experimental Medicine, 2002
709 citations recorded by the source corpus.
CD4+CD25+ regulatory T cells inhibit organ-specific autoimmune diseases induced by CD4+CD25−T cells and are potent suppressors of T cell activation in vitro. Their mechanism of suppression remains unknown, but most in vitro studies suggest that it is cell contact–dependent and cytokine independent. The role of TGF-β1 in CD4+CD25+ suppressor function remains unclear. While most studies have failed to reverse suppression with anti–transforming growth factor (TGF)-β1 in vitro, one recent study has reported that CD4+CD25+ T cells express cell surface TGF-β1 and that suppression can be completely abrogated by high concentrations of anti–TGF-β suggesting that cell-associated TGF-β1 was the primary effector of CD4+CD25+-mediated suppression. Here, we have reevaluated the role of TGF-β1 in CD4+CD25+-mediated suppression. Neutralization of TGF-β1 with either monoclonal antibody (mAb) or soluble TGF-βRII-Fc did not reverse in vitro suppression mediated by resting or activated CD4+CD25+ T cells. Responder T cells from Smad3−/− or dominant-negative TGF-β type RII transgenic (DNRIITg) mice, that are both unresponsive to TGF-β1–induced growth arrest, were as susceptible to CD4+CD25+-mediated suppression as T cells from wild-type mice. Furthermore, CD4+CD25+ T cells from neonatal TGF-β1−/− mice were as suppressive as CD4+CD25+ from TGF-β1+/+ mice. Collectively, these results demonstrate that CD4+CD25+ suppressor function can occur independently of TGF-β1.
Subfields: Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/9f7ce45d1277fd1b3db80ef7d92fbd875b5e43dc
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In Immunology
- E. Shevach
- W. Strober
- B. Beutler
- Shimon Sakaguchi
- Y. Belkaid
- C. Piccirillo
- I. Fuss
- Loise M. Francisco
In Oncology
Citations in the corpus
- An essential role for Scurfin in CD4+CD25+ T regulatory cells (2003, background): “, and data indicate that T R cells can function in the absence of TGF-β production or signalin”
- CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity (2002, background): “major infection in the skin are phenotypically and functionally identical to the naturally occurring CD4 p CD25 p regulatory T cell”
- TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. (2006, background): “Coculture of Naive CD4 T Cells with Treg in the Presence of LPS Induces IL-17 Production Coculture of naive CD4 T cells and Treg at a 1:1 ratio in the presence of DC and LPS abrogates the suppressive function of Treg on T cell proliferation, as previously shown ( Pasare and Medzhitov [2003] and Fig”
- Mechanisms of foxp3+ T regulatory cell-mediated suppression. (2009, result): “In contrast to these studies, Piccirillo et al. (2002) were unable to show a requirement for either the production of TGF-b or responsiveness to TGF-b in Treg cell-mediated suppression.”
- IL-2 Is Essential for TGF-β to Convert Naive CD4+CD25− Cells to CD25+Foxp3+ Regulatory T Cells and for Expansion of These Cells1 (2007, background): “First, although TGF- can induce peripheral CD4 CD25 cells to become Treg cells, this cytokine is not required for the generation of the thymic-derived subset (13).”