Pyran (MVE-5) reverses the inhibition of macrophage receptors for cytophilic antibody induced by soluble immune complexes.

Soluble antigen-antibody (Ag-Ab) complexes, composed of 3 M KCl-extracted leukemia L1210 antigens and antibody to L1210, given to C57B1/6 mice caused immunosuppression in the mice. This was reflected in part by (a) the inhibition of cytophilic antibody receptors on peritoneal macrophages and (b) decreased phagocytic activity of the macrophages. Pyran copolymer MVE-5 given to the mice either 4 h before, or 5 or 8 days after, the Ag-Ab complexes abrogated this suppression. Macrophages from MVE-5-treated mice attached cytophilic antibodies to L1210 to the same extent as normal macrophages, despite the concomitant or previous administration of immune complexes. Macrophages from normal or immune-complex-treated mice given MVE-5 were more phagocytic than their counterparts from groups not given MVE-5. All of these effects of MVE-5 required 3-5 days to become manifest. Thymocytes or spleen T cells from mice treated with Ag-Ab complexes adoptively transfer the suppression to normal syngeneic mice. Treatment of the mice with MVE-5 4 h before the immune complexes abrogated the ability of T cells to transfer the suppression. However, MVE-5 given 5 or 8 days after Ag-Ab complexes did not affect the adoptive transfer of suppression, even when the testing of macrophages in recipients of T cells was performed 10 days after transfer. Treatment of normal mice with MVE-5 enabled their spleen or thymus T cells to prevent, but not reverse, the inhibition of macrophages upon adoptive transfer. Thus, the transfer of T cells from MVE-5-treated mice antagonized suppression if performed 4 h before administering immune complexes, whereas such "activated" T cells were ineffective when transferred 5 or 8 days later. MVE-5 apparently prevented the generation of suppressor inducer T cells, but once generated, these cells could not be directly antagonized by MVE-5 or by T cells stimulated by this agent. MVE-5 significantly activated peritoneal macrophages in T-cell-depleted mice, as well as in normal mice. The ability to form cytophilic antibody-mediated rosettes and to kill syngeneic B16 melanoma cells were both enhanced in the T-cell-depleted mice. Pyran copolymer MVE-5 probably exerted direct effects on peritoneal macrophages and an indirect effect through T cells in overcoming the suppressive effects of Ag-Ab complexes on macrophages.