Macrophage-induced reversal of immunosuppression by leukemia viruses.

Suppression of the humoral immune response by several murine leukemia viruses has been well documented. However, the mechanism of suppressed immunoresponsiveness is not well characterized. Macrophages have been reported to be intimately involved in host-tumor relationships, and were therefore examined for their role in reversing suppression in two leukemia virus-induced tumor models. In vivo studies with the Friend leukemia virus (FL virus) were unsuccessful in demonstrating any role for stimulated peritoneal exudate (PE) cells, rich in macrophages, in restoration of antibody function in leukemic mice. However, in vitro studies with FL virus demonstrated that proteose-peptone stimulated PE cells from normal syngeneic mice in restricted numbers (1-3 x 10(5)), when added to 5 x 10(6) FL virus infected spleen cells, could partially restore immunity. Furthermore, using the Rowson-Parr virus (RP virus) model system it was shown that PE cells from RP virus-infected mice, as well as normal PE cells, were capable of restoring immunocompetence. Neither splenic adherent cells nor lymphoid cells from other tissues, when added to RP virus-infected spleen cells, were able to induce recovery of the immune response. In addition, treatment with antitheta serum plus complement had no effect on the ability of PE cells to restore immunity, implying that macrophages were solely responsible for reversal of immunosuppression. An alteration of antigen "processing" or "focusing" may be an important mechanism by which recovery of immune competence is achieved.