A key role for TGF-beta signaling to T cells in the long-term acceptance of allografts.
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.
Daley
Stephen R
SR
Therapeutic Immunology Group, Sir William Dunn School of Pathology, Oxford, United Kingdom.
Ma
Jianbo
J
Adams
Elizabeth
E
Cobbold
Stephen P
SP
Waldmann
Herman
H
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006085:Graft Survival / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014184:Transplantation, Homologous