Regulation of Macrophage Ia Expression In Vivo and In Vitro

Abstract

The expression of Ia antigens on macrophages is critical for their function as antigen-presenting cells (1,2). Since the ability of individual macrophages to synthesize and express Ia is short-lived (3,4), the control mechanisms regulating these events become of major importance. We have recently shown that, in vivo, the phenotype of the exudate macrophage can be regulated by immunologic stimuli, such as administration of hemocyanin, sheep erythrocytes, and especially the intracellular bacterium Listeria monocytogenes (5). With intra-peritoneal injection of Listeria, the level of local la-bearing macrophages (as determined by immunofluorescence) can reach 90% or more, while in normal mice, or mice given inflammatory stimuli such as peptone, it is only about 5 to 10%. All experiments reported here employed a monoclonal antibody (clone 10-2.16) recognizing specificities 17 of the I-A subregion of fkr and s haplotypes. Using another monoclonal antibody (against I-E/C) as well as A.TH anti A.TL antibodies, we have found that the response to modulation of I-A subregion determinants is characteristic of Ia antigens in general (4,7). This amplification of the la-positive subset was shown, by adoptive transfer, to require the function of activated T cells. Moreover, when peritoneal exudate cells from Listeria-immunized mice were cultured with heat-killed Listeria, they produced a soluble mediator which, when injected intraperitoneally into normal mice, induced a similar, selective augmentation of the la-positive population (6). The T cell origin of this activity has been confirmed by its production by T cell lines and hybridomas. It is not genetically restricted in its action, has a molecular weight of approximately 50,000 daltons, and is referred to as macrophage (la-positive)-recruiting factor (MIRF).