AGGREGATED IMMUNOGLOBULIN PROTECTS IMMUNE T-CELLS FROM SUPPRESSION - DEPENDENCE ON ISOTYPE, FC PORTION, AND MACROPHAGE FC-GAMMA-R

We determined the regulatory properties of heat-aggregated immunoglobu lins (HA-IE) that possess many activities of immune complexes (IC), su ch as binding and activation of cells via immunoglobulin Fc gamma rece ptors (Fc gamma R). HA-Ig protected contact sensitivity (CS) effector T cells from antigen-specific immunosuppression, while monomeric IgG w ere inactive. This anti-suppressive activity of HA-Ig was antigen nons pecific, and depended on the species from which Ig was derived, i.e. m ouse and rat HA-Ig were protective in mice, and of other species were inactive. The protecting activity of HA-Ig was confined to IgG2a and I gG3, and to a lesser degree to IgG1 isotypes, and resided in the Fc do main. Removal of phagocytic cells from the CS-immune target cells, or blocking with anti-Fc gamma R mAb, abolished HA-Ig protection of CS-ef fector T cells from suppression. We suggest that HA-Ig multimers acted via Fe domains, in one of two ways: by binding to Fc gamma R of macro phages to produce positive-acting cytokines, or by blocking Fc gamma R on macrophages, to compete with suppressive factors that can also bin d to Fc gamma R. If HA-Ig protection of T cells is generalized, it is likely that IC in vivo may non-specifically overcome suppression of re sponses to antigen that normally are under the control of T suppressiv e cells, and thus may contribute to the development of autoimmunity.