lymphokine, lymphocyte activation, peritoneum macrophage, protozoon, spleen
Soluble products from antigen stimulated Trypanosoma cruzi-immune spleen cells enhanced the expression of Ia antigens on proteose-peptone-elicited mouse peritoneal macrophages (Mphi). Acquisition of Ia paralleled Mphi activation, previously shown to be mediated by this same source of lymphokine (LK). Expression of Ia and four other plasma membrane antigens was monitored by quantitative binding and radioautographic studies with 125I-monoclonal antibodies. Immune LK selectively enhanced expression of Ia and, to a lesser extent, H-2D relative to control LK from antigen-stimulated noninfected spleen. The levels of three other non-major histocompatibility complex (MHC) antigens, including the trypsin-resistant Fc receptor, were similar in cells exposed to both sources of LK. As little as 1% immune LK induced one-half maximal expression of Ia. Kinetic studies revealed that much of the Ia on freshly explanted peritoneal Mphi was lost during the 1st d of culture. In the continued presence of immune LK, Ia was re-expressed on virtually all Mphi by the 2nd and 3rd d. Alternatively, >95% Ia negative populations were obtained by culturing the cells 3 d; then, addition of LK induced Ia on most cells within 1 d. Once induced, Ia persisted on the Mphi surface for at least 2 d. [ 35S]methionine radiolabeling indicated that immune LK selectively increased radiolabeling of Mphi Ia, again with other non-MHC-linked plasma membrane polypeptides as controls. LK-induced Ia-bearing Mphi were tested as primary mixed leukocyte reaction stimulators. 1 x 10 5-2 x 10 5 Mphi did not stimulate 4.5 x 10 6 responding T cells, whereas 1 x 10 4 dendritic cells induced strong responses, as previously described. Because Ia-positive Mphi do not actively sensitize T cells in a model immune response, we propose that Mphi MHC products serve primarily as recognition sites for previously sensitized T cells, thereby enhancing T cell-mediated Mphi activation.
Steinman, R. M., N. Nogueira, M. D. Witmer, J. D. Tydings, and I. S. Mellman. 1980. "Lymphokine Enhances the Expression and Synthesis of Ia Antigens on Cultured Mouse Peritoneal Macrophages." Journal of Experimental Medicine 152 (5): 1248-1261