Effect of selective T cell depletions in mixed xenogeneic reconstitution on specific hyporeactivity to transplantation across a species barrier.

We have recently reported the induction of long-term specific hyporeactivity to transplantation across a species barrier (rat----mouse) through reconstitution of irradiated recipients with a mixture of T-cell-depleted host-type C57BL/10Sn (B10) bone marrow plus T-cell-depleted F344 rat bone marrow (B10+F344----B10) (1). We report here the influence of selective T cell depletions of host-type and/or donor-type bone marrow on induction of such hyporeactivity. Mice that received mixed bone marrow inocula in which the syngeneic marrow had been T-cell-depleted, whether or not the xenogeneic donor marrow had been treated, showed specific prolongation of F344 donor-type skin grafts. In contrast, F344 rat skin grafts were promptly rejected by animals that had received mixed bone marrow inocula in which the syngeneic component had not been T-cell-depleted. Serologic reactivity against F344 lymphocyte cell surface antigens also differed among the four groups; animals that had received untreated syngeneic bone marrow demonstrated high levels of reactivity to F344 target cells, while animals reconstituted with mixed inocula in which the syngeneic component had been T-cell-depleted exhibited low levels, if any, of serologic reactivity against F344 splenocytes. This model for mixed xenogeneic reconstitution may be helpful to define the conditions required for induction of transplantation tolerance across a species barrier.