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Cell Contact–Dependent Immunosuppression by Cd4+Cd25+Regulatory T Cells Is Mediated by Cell Surface–Bound Transforming Growth Factor β
Open accessAbstract
CD4+CD25+ T cells have been identified as a population of immunoregulatory T cells, which mediate suppression of CD4+CD25− T cells by cell–cell contact and not secretion of suppressor cytokines. In this study, we demonstrated that CD4+CD25+ T cells do produce high levels of transforming growth factor (TGF)-β1 and interleukin (IL)-10 compared with CD4+CD25− T cells when stimulated by plate-bound anti-CD3 and soluble anti-CD28 and/or IL-2, and secretion of TGF-β1 (but not other cytokines), is further enhanced by costimulation via cytotoxic T lymphocyte–associated antigen (CTLA)-4. As in prior studies, we found that CD4+CD25+ T cells suppress proliferation of CD4+CD25− T cells; however, we observed here that such suppression is abolished by the presence of anti–TGF-β. In addition, we found that CD4+CD25+ T cells suppress B cell immunoglobulin production and that anti–TGF-β again abolishes such suppression. Finally, we found that stimulated CD4+CD25+ T cells but not CD4+CD25− T cells express high and persistent levels of TGF-β1 on the cell surface. This, plus the fact that we could find no evidence that a soluble factor mediates suppression, strongly suggests that CD4+CD25+ T cells exert immunosuppression by a cell–cell interaction involving cell surface TGF-β1.
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“In preliminary studies we determined the expression of CTLA-4 in CD4 CD25 T cells, both with respect to cell surface and intracellular CTLA-4, as the majority of CTLA-4 protein resides in the cytoplasm (20).”
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Metadata
- Authors
- Nakamura, K., Kitani, A., & Strober, W.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2001-09-03
- Volume
- 194
- Issue
- 5
- Pages
- 629-644
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2161545566
- Cited by
- 1,594
- References
- 2
- FWCI
- 26.70
- Type
- journal article
- Language
- en
- Open access
- bronze
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