Variations in macrophage antigen phenotype: a correlation between Ia antigen reduction and immune dysfunction during tumor growth.

Abstract

Variable Ia antigen expression by macrophages (M phi) was examined during tumor growth by measuring: Ia antigen masking and immunofluorescence by anti-Ia antibody, accessory cell function in concanavalin A (Con A) and mixed lymphocyte reaction (MLR)-induced T cell proliferation, and M phi stimulatory function in the MLR. Tumor-induced progressive loss of Ia antigen expression was shown by immunofluorescence and corroborated by anti-Ia blockade of MLR stimulatory activity of normal but not tumor-bearing hosts (TBH) splenic M phi. The TBH splenic M phi supported Con A-induced proliferation of syngeneic T cells (Ia antigen-independent) but did not support syngeneic T cell proliferation in the MLR (Ia antigen-dependent). Irrespective of tissue source, normal and TBH M phi differed in their MLR stimulatory capabilities. In general, splenic M phi preparations were better stimulators of allogeneic T cell blastogenesis in the MLR than thioglycollate-elicited peritoneal M phi. Kinetic studies with TBH M phi showed a significant progressive loss in MLR stimulatory activity, which was especially pronounced with peritoneal M phi. Expression of Ia antigens by normal but not TBH M phi were diminished by 24-h in vivo plating of the peritoneal M phi. Indomethacin treatment showed Prostaglandin E2 was not a direct in vitro factor in Ia antigen-mediated reduction of splenic M phi MLR stimulatory activity. Taken together, these data delineate a loss of M phi Ia antigen expression, resulting in a decrease in Ia antigen-mediated functional activities during tumor growth.