Farnesyl transferase inhibitors delay primary skin allograft rejection in class II MHC‐mismatched mice

Abstract

Listen

Translate article

We are investigating the possibility that farnesyl transferase inhibitors (FTIs) may be useful anti‐rejection drugs. We have shown that the FTI, L‐744,832 can significantly delay allograft rejection in mice using MHC class II mismatched skin allografts. When treatment with this FTI begins two days prior to the allograft procedure and extends for 5 days, we found that rejection was delayed in all treated mice, 26±14 days, compared to untreated mice, 13±4 days. Interestingly, this delay in rejection can extend for greater than 30 days in 30% of the treated mice. To determine whether FTI treatment can delay alloreactive effector responses, we examined the effect of L‐744,832 treatment on allograft rejection in mice that had previously been sensitized to the allo‐antigens. We found that treatment with this FTI did not significantly delay second‐set allograft rejection. This observation, coupled with the long delay in some of the first set allograft treatments, suggests that FTIs may be able to induce tolerance of the alloreactive CD4+ T cells. To further investigate the action of FTIs on graft rejection we are measuring the effects of treatment using mixed lymphocyte cultures and using in vivo tolerance assays. We suggest that FTIs may modulate acute immune responses without systemically suppressing the immune system.