Alloimmunization-activated suppressor cells. I: Abrogation of lethal graft-versus-host reaction directed against non-H-2 antigens

Abstract

Incompatibility for DBA/2 (D2) minor histocompatibility antigens (MiHA) alone leads to a severe lethal graft-versus-host reaction (GVHR) in adult (D2 X B10.D2)F1 recipients of B10.D2 bone marrow and spleen cells. In this genetic combination, mortality is completely abrogated by preimmunization of the graft donor against unrelated H-2b antigens and specific D2 MiHA a short time before grafting. Protection against GVHR mortality is elicited by immunizing the donors with a single transfusion of incompatible spleen cells or whole blood. Abrogation of GVHR mortality is due mainly to the immunization with specific MiHA, and only to a much lesser degree to the immunization with unrelated H-2 antigens; the protective effect induced by association of these two types of immunization, however, is significantly better than that elicited by either type of immunization alone. It is unlikely that this abrogation of GVHR mortality results from "dilution" of specifically reactive cells; rather, suppressor cells appear to be a contributing factor, because the preimmunization activates, in the donor spleen, suppressor cells capable of decreasing the severity of the GVHR developed against MiHA by normal cells. Histopathologic observations indicated that the lesions induced in various tissues after grafting of preimmunized donor cells were considerably less severe than those induced by grafting of normal donor cells. However, simultaneous immunization with specific MiHA and unrelated H-2 antigens may also exacerbate the GVHR, depending upon the conditions used for preimmunization; abrogation of GVHR mortality is favored by a single immunization with unrelated H-2b antigens and specific MiHA administered simultaneously a short time before grafting, whereas an acceleration of GVHR mortality is favored by long intervals and multiple immunizations. It is suggested that, depending upon the conditions used for the preimmunization, the allogeneic effect produced by stimulation with unrelated H-2 antigens may augment the response to MiHA or it may enhance the activation of suppressor cells that contribute to the abrogation of GVHR mortality.