1782 LYMPHOKINE REGULATION OF MACROPHAGE Ia ANTIGEN EXPRESSION Gel Filtration Chromatography

The initiation of many antigen-specific, T-dependent immune responses requires the participation of accessory cells that express Ia antigens (1, 2). Recent evidence indicates that the Ia antigen expression of macrophages, a principle class of accessory cells, is regulated by lymphokines: Ste inman et al. (3) have reported that culture supernatants of Trypanosoma cruzi-activated spleen cells enhanced the synthesis and expression of Ia antigens by murine macrophages in vitro. Steeg et al. (4) have observed that culture supernatants of concanaval in A-stimulated spleen cells (Con A supernatant) 1 induced Ia murine thioglycollate-elicited peritoneal exudate macrophages to express Ia antigens in vitro. Macrophages incubated with lymphokinecontaining culture supernatants developed the capacity to initiate the mixed leukocyte reaction (4) and the antigen-specific activation of helper T lymphocytes (5, 6). Finally, Scher et al. (7) have reported that intraperitoneal injections of culture supernatants of Listeria monocytogenes-stimulated lymphocytes induced peritoneal exudates that are enriched in Ia + macrophages. Identification of the lymphokine(s) that modulates macrophage Ia antigen expression has been hampered by the plethora of lymphokine activities present in relatively low titers and high-protein contents of the lymphokine-containing culture supernatants. This paper characterizes the macrophage Ia antigen regulatory mediator present in the Con A supernatant and demonstrates that the macrophage Ia antigen regulatory mediator shares antigenic (8) and biochemical characteristics with immune interferon (IFN-7). Furthermore, independently prepared IFN-y, purified to 10 7 U / mg protein specific activity, both induced and maintained macrophage Ia antigen