Variations in Macrophage Antigen Phenotype: A Correlation Between Ia Antigen Reduction and Immune Dysfunction During Tumor Growth

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