Cd8 T cell-mediated rejection of intestinal allografts is resistant to inhibition of the CD40/CD154 costimulatory pathway

Background. Disruption of the CD40/CD154 pathway inhibits rejection in nume rous models. The importance of this pathway on intestinal allograft rejecti on was examined in this study. Methods. Intestinal grafts from B6C3F1 mice transplanted into C57BL/6 recip ients were assessed histologically for rejection. Results. The monoclonal antibody to CD154, MR1, failed to inhibit rejection in wild-type mice. Similarly, CD154(-/-) recipient mice rejected intestina l allografts. MR1 did inhibit early rejection in CD8(-/-) mice, but had no effect in CD4(-/-) recipients. AU MR1-treated CD8(-/-) recipients eventuall y developed rejection, No benefit was observed when blockade of the CD40/CD 154 pathway by MR1 was combined with blockade of the CD28/B7 pathway by mCT LA4Ig. Conclusions. These data suggest that CD4(+) T cells mediating intestinal al lograft rejection may be more dependent upon the CD40/CD154 pathway than CD 8(+) T cells. This finding highlights the importance of identifying agents that suppress CD8(+) T cell-mediated rejection.