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CD4(+)CD25(+) regulatory T (T reg) cells play a pivotal role in control of the immune response. Transforming growth factor-beta (TGF-beta) has been shown to be required for T reg cell activity; however, precisely how it is involved in the mechanism of suppression is poorly understood. Using the T cell transfer model of colitis, we show here that CD4(+)CD45RB(high) T cells that express a dominant negative TGF-beta receptor type II (dnTbetaRII) and therefore cannot respond to TGF-beta, escape control by T reg cells in vivo. CD4(+)CD25(+) T reg cells from the thymus of dnTbetaRII mice retain the ability to inhibit colitis, suggesting that T cell responsiveness to TGF-beta is not required for the development or peripheral function of thymic-derived T reg cells. In contrast, T reg cell activity among the peripheral dnTbetaRII CD4(+)CD25(+) population is masked by the presence of colitogenic effector cells that cannot be suppressed. Finally, we show that CD4(+)CD25(+) T reg cells develop normally in the absence of TGF-beta1 and retain the ability to suppress colitis in vivo. Importantly, the function of TGF-beta1(-/-) T reg cells was abrogated by anti-TGF-beta monoclonal antibody, indicating that functional TGF-beta can be provided by a non-T reg cell source.

Type

Journal article

Journal

The Journal of experimental medicine

Publication Date

03/2005

Volume

201

Pages

737 - 746

Addresses

Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, England, UK.

Keywords

Spleen, Thymus Gland, CD4-Positive T-Lymphocytes, Th1 Cells, Animals, Mice, Knockout, Mice, Colitis, Transforming Growth Factor beta, Receptors, Interleukin-2, Cytokines, Cell Differentiation, Immune Tolerance, Transforming Growth Factor beta1