T cells that cannot respond to TGF-beta escape control by CD4(+)CD25(+) regulatory T cells.

Journal article

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.

Authors: Fahlén, L; Read, S; Gorelik, L; Hurst, S; Coffman, R

• Publication status: Published
• Journal: Journal of experimental medicine
• Volume: 201
• Issue: 5
• Pages: 737-746
• Publication date: 2005-03-01
• DOI: 10.1084/jem.20040685
• EISSN: 1540-9538
• ISSN: 0022-1007
• Language: English
• Keywords: Cell Differentiation; Mice; Transforming Growth Factor beta1; Thymus Gland; Spleen; Animals; Th1 Cells; Transforming Growth Factor beta; Cytokines; CD4-Positive T-Lymphocytes; Mice, Knockout; Receptors, Interleukin-2; Colitis; Immune Tolerance