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

• Published in: The Journal of experimental medicine Vol. 201; no. 5; pp. 737 - 746
• Main Authors: Fahlen, Linda, Read, Simon, Gorelik, Leonid, Hurst, Stephen D, Coffman, Robert L, Flavell, Richard A, Powrie, Fiona
• Format: Journal Article
• Language: English
• Published: 07.03.2005
• ISSN: 0022-1007; 1892-1007

CD4 super(+)CD25 super(+) 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 super(+)CD45RB super(high) T cells that express a dominant negative TGF- beta receptor type II (dnT beta RII) and therefore cannot respond to TGF- beta , escape control by T reg cells in vivo. CD4 super(+)CD25 super(+) T reg cells from the thymus of dnT beta RII 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 dnT beta RII CD4 super(+)CD25 super(+) population is masked by the presence of colitogenic effector cells that cannot be suppressed. Finally, we show that CD4 super(+)CD25 super(+) T reg cells develop normally in the absence of TGF- beta 1 and retain the ability to suppress colitis in vivo. Importantly, the function of TGF- beta 1 super(-/-) 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.