Injection of v-mos-transformed and irradiated macrophages leads to longlasting specific acceptance of MHC-allogeneic heart grafts and specific prolongation of skin graft survival in mice.

Abstract

In vitro studies have revealed that the v-mos-transformed clone mos2 (mos2) of the murine macrophage cell line P388D1 (D1) (H-2d) is capable of inducing a state of specific unresponsiveness in MHC-allogeneic unprimed T cells. Here, we present data on the in vivo relevance of these findings. Male C57bl/6 mice (H-2b) were injected i.p. 6 times with 10(7) of the following irradiated cell types: D1, mos3, mos2, DBA/2-(H-2d) or C3H-(H-2k) spleen macrophages. DBA/2 and C3H skin or heart grafts were performed 10 days after the last injection. The normal rejection time for allogeneic skin was 7.5 days and for allogeneic hearts, was 12.8 days. After injection of D1 or mos3, DBA/2 skin grafts were rejected after 4.5 and 6.5 days, respectively, and the hearts, after 15.4 and 18.6 days, respectively. Third-partly C3H grafts were rejected normally (7.0 days). In contrast, injection of mos2 led to prolongation of DBA skin graft survival to 12.3 days. DBA/2 hearts were accepted for more than 160 days as revealed by heart beating. Again, C3H grafts were rejected normally (11.0 days). DBA/2 skin grafts on day 102 after heart grafting survived for 30 days, indicating hyporesponsiveness against these grafts. These results confirmed the in vitro findings. The mos2 cells obviously induced a state of specific unresponsiveness in otherwise unmanipulated recipients. However, the duration of this unresponsiveness induced by the injection of irradiated cells was dependent on the organ type.