This research proposal investigates the regulation of the development and tissue distribution of Ia-bearing macrophages. We have shown that immunological stimulation of peritoneal T cells causes a rapid and preferential influx of Ia-bearing macrophages into the peritoneal exudate. More recently, we have described a soluble mediator with similar activity. This factor is produced in culture during the antigen-dependent interaction of primed T cells and macrophages; injected intraperitoneally, it changes the composition of the exudate from 5 to 10% Ia-positive macrophages to 50 to 70%. This proposal is concerned primarily with evaluating the factor. We want, first, to study the immunological events leading to the production of the factor; second, to characterize the molecule(s) biochemically and purify them; and lastly, to analyze the factors's model of action. Concerning the last issue, we will evaluate whether the mediator affects macrophage kinetics in vivo, as well as the production and maturation of bone marrow macrophage in vivo and in vitro; whether it may have direct effects regulating Ia biosynthesis, and if it acts as a chemoattractant. We wish to characterize the target cell of the factor as to its surface phenotype, developmental stage, tissue distribution, and possible binding of the factor. Finally, we will evaluate the potential advantage to animals with increased levels of Ia-positive macrophages in responding to protein antigens and bacterial infection. The studies also include the evaluation of non-immune stimuli known to induce exudates in which the macrophages are primarily Ia-negative. A second part of the proposal evaluates the marked difference in the distribution of Ia-positive macrophages in different tissues; our findings range from 5 to 10% Ia-positive in the peritoneum to 70% in the thymus. We will test for molecules within the tissues that may control these differences and for the presence of local precursor cells that may differentiate to express Ia in suitable microenvironments.