Rao V S, Mitchell M S
J Biol Response Mod. 1983;2(1):67-80.
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.
由3M氯化钾提取的白血病L1210抗原与L1210抗体组成的可溶性抗原-抗体（Ag-Ab）复合物给予C57B1/6小鼠后会导致小鼠免疫抑制。这部分体现在：（a）抑制腹膜巨噬细胞上的嗜细胞抗体受体；（b）降低巨噬细胞的吞噬活性。在给予Ag-Ab复合物前4小时、或后5天或8天给予小鼠吡喃共聚物MVE-5可消除这种抑制作用。尽管同时或先前给予了免疫复合物，但来自MVE-5处理小鼠的巨噬细胞与正常巨噬细胞一样能将嗜细胞抗体附着到L1210上。给予MVE-5的正常或免疫复合物处理小鼠的巨噬细胞比未给予MVE-5组的对应巨噬细胞吞噬能力更强。MVE-5的所有这些作用需要3至5天才能显现出来。用Ag-Ab复合物处理的小鼠的胸腺细胞或脾T细胞可将这种抑制作用过继转移给正常同基因小鼠。在免疫复合物处理前4小时用MVE-5处理小鼠可消除T细胞转移抑制作用的能力。然而，在Ag-Ab复合物处理后5天或8天给予MVE-5并不影响抑制作用的过继转移，即使在T细胞受体小鼠中对巨噬细胞进行检测是在转移后10天进行。用MVE-5处理正常小鼠可使其脾或胸腺T细胞在过继转移时预防但不能逆转巨噬细胞的抑制作用。因此，如果在给予免疫复合物前4小时进行转移，来自MVE-5处理小鼠的T细胞转移可对抗抑制作用，而在5天或8天后转移时，这种“活化”的T细胞则无效。MVE-5显然可阻止抑制诱导T细胞的产生，但一旦产生，这些细胞不能被MVE-5或受该药物刺激的T细胞直接对抗。MVE-5可显著激活T细胞耗竭小鼠以及正常小鼠的腹膜巨噬细胞。T细胞耗竭小鼠形成嗜细胞抗体介导的玫瑰花结和杀伤同基因B16黑色素瘤细胞的能力均增强。吡喃共聚物MVE-5在克服Ag-Ab复合物对巨噬细胞的抑制作用方面可能对腹膜巨噬细胞有直接作用，并通过T细胞有间接作用。
