Long-term survival of skin allografts induced by donor splenocytes and anti-CD154 antibody in thymectomized mice requires CD4 (+) T cells, interferon-gamma, and …

TG Markees, NE Phillips, EJ Gordon… - The Journal of …, 1998 - Am Soc Clin Investig
TG Markees, NE Phillips, EJ Gordon, RJ Noelle, LD Shultz, JP Mordes, DL Greiner…
The Journal of clinical investigation, 1998Am Soc Clin Investig
Treatment of C57BL/6 mice with one transfusion of BALB/c spleen cells and anti-CD154
(anti-CD40-ligand) antibody permits BALB/c islet grafts to survive indefinitely and BALB/c
skin grafts to survive for approximately 50 d without further intervention. The protocol
induces long-term allograft survival, but the mechanism is unknown. We now report:(a)
addition of thymectomy to the protocol permitted skin allografts to survive for> 100 d,
suggesting that graft rejection in euthymic mice results from thymic export of alloreactive T …
Treatment of C57BL/6 mice with one transfusion of BALB/c spleen cells and anti-CD154 (anti-CD40-ligand) antibody permits BALB/c islet grafts to survive indefinitely and BALB/c skin grafts to survive for approximately 50 d without further intervention. The protocol induces long-term allograft survival, but the mechanism is unknown. We now report: (a) addition of thymectomy to the protocol permitted skin allografts to survive for > 100 d, suggesting that graft rejection in euthymic mice results from thymic export of alloreactive T cells. (b) Clonal deletion is not the mechanism of underlying long-term graft survival, as recipient thymectomized mice were immunocompetent and harbor alloreactive T cells. (c) Induction of skin allograft acceptance initially depended on the presence of IFN-gamma, CTLA4, and CD4(+) T cells. Addition of anti-CTLA4 or anti-IFN-gamma mAb to the protocol was associated with prompt graft rejection, whereas anti-IL-4 mAb had no effect. The role of IFN-gamma was confirmed using knockout mice. (d) Graft survival was associated with the absence of IFN-gamma in the graft. (e) Long-term graft maintenance required the continued presence of CD4(+) T cells. The results suggest that, with modification, our short-term protocol may yield a procedure for the induction of long-term graft survival without prolonged immunosuppression.
The Journal of Clinical Investigation