Regulation of murine macrophage Ia-antigen expression by products of activated spleen cells.

Abstract

This investigation examined the effects of mediators derived form activated spleen cells on macrophage Ia-antigen expression and function. Incubation of adherent thioglycollate-induced murine peritoneal macrophages(> 90% Ia-) with concanavalin A (Con A)-stimulated spleen cell supernate (Con A sup) resulted in a dose-dependent increase in the percentage of Ia-containing (Ia+) phagocytic cells, as detected by antiserum-and-complement-mediated cytotoxicity. The Ia-antigen expression of macrophages incubated with unstimulated spleen cell supernate supplemented with Con A (Control sup) declined. Pretreatment of the macrophages with anti-Ia and complement before addition of the Con A sup did not inhibit subsequent Ia-antigen expression, suggesting that Ia- macropohages were converted to Ia+ cells. These findings were not a result of adsorption of soluble Ia-antigen from the Con A sup, because Ia-antigen expression was detected by an antiserum specific for the haplotype of the macrophages but not that of the allogeneic spleen cells from which the supernate was prepared. Con A sup-cultured macrophages also stimulated the proliferation of allogeneic spleen cells significantly better than Control sup-cultured macrophages in the mixed leukocyte reaction (MLR). Pretreatment of Con A sup-cultured macrophages with anti-Ia and complement before addition of splenic responder cells abrogated their stimulatory capacity, indicating the Ia dependence of the MLR. We hypothesize that regulatory lymphokine(s) can induce both the expression of the Ia+ phenotype by macrophages and the functional capability to stimulate the MLR, and that macrophages lose these capabilities in the absence of such mediator(s).

Relationship of Cell-Cycle Expression of Ia-like Antigenic Determinants on Normal and Leukemia Human Granulocyte-Macrophage Progenitor Cells to Regulation In Vitro by Acidic Isoferritins

“…This suggested either that the acidic isoferritins were being inactivated within a few hours within the cultures or that with time in culture the CFU-GM became insensitive to the actions of acidic isoferritins even though they were preceding through S-phase. In the absence of certain exogenously added agents the biosynthesis and surface expression of Ia-antigens on mouse peritoneal macrophages is terminated during the 1st d in culture (23)(24)(25). This work suggested a testable hypothesis that CFU-GM were losing their Ia antigens with time in culture and were therefore insensitive to the actions of acidic isoferritins.…”

“…Neither of the two reappeared within 24 h in culture under the conditions used in the present studies. Shedding of Ia-antigens from mouse macrophages is known to occur within a few hours when cells are placed at 37°C (23)(24)(25) but, until purified populations of human CFU-GM are obtained it will not be possible to examine the actual synthesis and shedding of Ia-antigens from these cells, and to confirm the indirect evidence obtained by the complement-dependent cytotoxicity tests. Recent evidence by L. M. Pelus4 has implicated E type prostaglandins (PGE1,2) in the "induction" of the responsiveness of a portion of human CFU-GM to killing by anti-Ia (mNEI-011, mBD, or mOKlal) plus complement and to inhibition by acidic isoferritins after 24, but not after 6 h, in culture at 37°C if PGE is present in the culture at time zero.…”

Differential expression of Ia molecules by human monocytes.

“…This suggests that not only may there be discoordinate expression of HLA-DR and HLA-DC in normal MO but that the regulatory signals governing expression of these Ia antigens may be different. Studies in the murine system have demonstrated that both I-A and I-E can be induced by a soluble factor released by activated T cells (16)(17)(18)(19)(20)(21). One of these factors has been demonstrated to be IFN-'y (22)(23).…”

The extracellular domain of the human interferon gamma receptor interacts with a species-specific signal transducer.

“…We conclude that the extracellular domain of the IFN-,y receptor is involved not only in the species specificity of IFN-,y binding but also in signalling through interaction with an as yet unidentified species-specific factor(s) encoded by a gene(s) on human chromosome 21. Interferon gamma (IFN-y) is a cytokine produced by activated T cells and natural killer cells that has antiviral and antiproliferative effects on a wide variety of cells (53). Its most potent effects are immunomodulatory (50) and include the activation of macrophages (46), the regulation of major histocompatibility complex (MHC) class I and class II antigen expression (31,49), and the regulation of immunoglobulin production (35,48).…”