IMMUNOSUPPRESSIVE ACTIVITY OF MACROPHAGES IN MICE UNDERGOING GRAFT-VERSUS-HOST REACTION DUE TO MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I PLUS CLASS-II DIFFERENCE

In a previous report, we showed that the injection of parental CD4+ T cells into major histocompatibility complex (MHC) class II disparate F1 hybrid mice induces autoimmune-like graft versus-host reaction (GVHR) resembling systemic lupus erythematosus (SLE) and the hepatic lesion of primary biliary cirrhosis (PBC). In the present study, we examined whether or not simultaneous or subsequent injection of CD8+ T cells changes the GVH R form. When parental CD8+ T cells together with CD4+ T cells were injected into MHC class I plus class II-disparate F1 mice, autoimmune phenomena did not develop and alternatively a profound immunosuppressive state was induced. Furthermore, ongoing autoimmune-like GVHR induced by CD4+ T cells was also suppressed by later injection of CD8+ T cells. In these mice, an increase of donor type CD8+ T cells and a marked decrease of host B and T cells in the spleen were observed. The spleen cells from these mice strongly inhibited the mitogenic response of normal spleen cells against lipopolysaccharide (LPS). In vitro studies demonstrated that this immunosuppression was not induced by CD8+ T cells themselves but by macrophages which produced suppressive factor(s) by LPS stimulation. These findings were discussed with reference to suppressive mechanisms of GVHR.