Loss of F1 hybrid resistance to bone marrow grafts after injection of parental lymphocytes. Demonstration of parental anti-F1 T killer cells and general immunosuppression in the host.

B6D2F1 mice acutely reject parental C57Bl/6 bone marrow grafts, a phenomenon that is known as hybrid resistance. Injection of C57Bl/6 splenocytes into B6D2F1 recipients prior to bone marrow transplantation had previously been shown to facilitate growth of C57Bl/6 marrow grafts. We show in this report that for this effect to occur, radiation-sensitive T cells have to be present in the splenocyte inoculum. Loss of hybrid resistance following injection of C57Bl/6 splenocytes into B6D2F1 mice coincides with the appearance of T killer cells of C57Bl/6 origin that are specific for H-2 histocompatibility antigens of DBA/2. The parental T killer cells in unresponsive B6D2F1 mice express in vitro cytotoxic activity on H-2d targets and appear to be responsible for the acquired in vivo rejection of H-2d bone marrow grafts. Appearance of donor-derived T killer cells coincides with marked suppression of host immunity: lymphocytes from unresponsive B6D2F1 mice do not proliferate in mixed lymphocyte reactions and fail to respond to sheep erythrocytes in vitro, nor do they express natural killer (NK) activity. Concomitant with the suppression of NK activity, hybrid resistance to C57B1/6 marrow grafts disappears. This loss of resistance to bone marrow transplants is unspecific since third-party SJL marrow grafts are not rejected. It is concluded that suppression of hybrid resistance by injection of parental splenocytes into B6D2F1 mice is caused by a severe nonspecific suppression of host immune responsiveness by parental T cells that recognize disparate histocompatibility antigens in the host.