Aggregated immunoglobulin protects immune T cells from suppression: dependence on isotype, Fc portion, and macrophage FcgammaR.
We determined the regulatory properties of heat-aggregated immunoglobulins (HA-Ig) that possess many activities of immune complexes (IC), such as binding and activation of cells via immunoglobulin Fc gamma receptors (FcgammaR). HA-Ig protected contact sensitivity (CS) effector T cells from antigen-specific immunosuppression, while monomeric IgG were inactive. This anti-suppressive activity of HA-Ig was antigen non-specific, and depended on the species from which Ig was derived, i.e. mouse 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 IgG3, and to a lesser degree to IgG1 isotypes, and resided in the Fc domain. Removal of phagocytic cells from the CS-immune target cells, or blocking with anti-FcgammaR mAb, abolished HA-Ig protection of CS-effector T cells from suppression. We suggest that HA-Ig multimers acted via Fc domains, in one of two ways: by binding to FcgammaR of macrophages to produce positive-acting cytokines, or by blocking FcgammaR on macrophages, to compete with suppressive factors that can also bind to FcgammaR. If HA-Ig protection of T cells is generalized, it is likely that IC in vivo may non-specifically overcome suppression of responses to antigen that normally are under the control of T suppressive cells, and thus may contribute to the development of autoimmunity.
Ptak
W
W
Department of Immunology, College of Medicine, Jagiellonian University, Cracow, Poland.
Paliwal
V
V
Bryniarski
K
K
Ptak
M
M
Askenase
P W
PW
D000818:Animals; D006361:Heating; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D010586:Phagocytes / Q000276:immunology; D011817:Rabbits; D051381:Rats; D011961:Receptors, Fc / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014407:Tumor Cells, Cultured
D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D011961:Receptors, Fc