Distinct populations of antigen-presenting macrophages are required for induction of effector and regulatory cells in contact sensitivity response in mice

Macrophages (Mf) and other antigen-present- mg cells (APCs) are able to induce both immune and regulatory T cells. We compared the antigen-presenting activities of different subpopulations of thioglycolate-in- duced peritoneal macrophages from mice that were or were not treated with cyclophosphamide (CY) by several functional (adherence and phagocytosis) and mor- phologic (phenotypic) markers (FcR, Ia). Different sub- populations of macrophages were derivatized with frmnitrophenyl and injected intravenously into recipients, which were tested directly for a contact sensitivity (CS) reaction or for the presence of efferent suppressor T (Ts) cells in passive transfer experiments. Our results demonstrate that peritoneal macrophages are both mor- phologicaJly and functionally heterogeneous. Macro- phages that induce immune cells that mediate CS have characteristics different from those that induce Ts cells. They accumulate in the low-density cell fraction on a dis- continuous Ficoll gradient, are insensitive to treatment in vivo with low doses of CY, phagocytose poorly and ad- here to plastic, and perhaps have low expression of FcRI and FcRII. Both macrophage fractions seem not to differ in expression of la, Mac-I, and Mac-3 antigens. It is ar- gued that low doses of CY abrogate suppression in vivo by selective action on Ts cells. Our results confirm that at least a portion of the action of CY may be due to its in- fluence on certain subpopulations of APCs. J. Leukoc. Biol. 53: 320-326; 1993.