Abrogation of alloreactive spleen cell-induced second-set skin graft rejection in mice with donor-specific bone...

To study the mechanism of induction of specific unresponsiveness to allografts in animals treated with antilymphocyte serum and donor bone marrow cells, we examined the effect of donor BMC on second-set graft rejection responses caused by antidonor-sensitized spleen cells (SSC) in mice bearing donor ear skin grafts. Anti-C3H SSC were obtained from skin-grafted, ALS-treated B6AF1 mice after rejection of their grafts. The second-set rejections of C3H skin grafts were assessed in B6AF1 mice following adoptive i.v. transfer of 30 x 10(6) SSC one day after grafting. Median survival time (MST) of C3H skin grafts in the group injected with SSC was 7 days, which is significantly lower than an MST of 11 days observed in the control group, which exhibited a first-set graft rejection response. Addition of 50 x 10(6) C3H BMC to 30 x 10(6) SSC abrogated the second-set rejection of C3H skin grafts (MST = 11 days). This abrogation effect of BMC is strain-specific, since BMC of a third-party strain (DBA/2) failed to abrogate the second-set rejection responses caused by anti-C3H SSC. Of the different C3H lymphoid cells tested for abrogation of the second-set graft rejection, BMC were the most effective. Splenocytes were more effective than thymocytes, which showed a partial effect. Lymph node cells had no effect. Our data suggest that unresponsiveness to allografts in animals treated with the ALS/bone marrow protocol may result from the inactivation of graft-reactive cells by donor BMC.