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TGF-beta is a key immunoregulatory cytokine which supports self-tolerance by signaling to T cells. In this report, we show a crucial role for TGF-beta signaling to T cells in enabling the long-term acceptance of allografts, whether natural or induced therapeutically by coreceptor and costimulation blockade. The requirement for TGF-beta appears most pronounced during the initial exposure to alloantigens. We demonstrate the ability of TGF-beta to direct the development in vitro of regulatory cells that suppress graft rejection in vivo. Such suppression was not affected by anti-TGF-beta treatment of the recipient mice. Despite this, TGF-beta may still have a role in CD4+ cell-mediated suppression of antiallograft responses in vivo, since its neutralization can, in some cases, abrogate suppression. These results show that TGF-beta signaling to T cells is dispensable for mounting destructive responses against skin allografts while appearing to be an essential intermediary in establishing long-term tolerance.

Type

Journal article

Journal

J Immunol

Publication Date

15/09/2007

Volume

179

Pages

3648 - 3654

Keywords

Amino Acid Sequence, Animals, Cells, Cultured, Female, Graft Survival, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Knockout, Mice, Transgenic, Molecular Sequence Data, Signal Transduction, Skin Transplantation, T-Lymphocytes, Transforming Growth Factor beta, Transplantation, Homologous