Antibody penetration into living cells. II. Anti-ribonucleoprotein IgG penetrates into Tgamma lymphocytes causing their deletion and the abrogation of suppressor function.
We have previously shown that an anti-ribonucleoprotein (RNP) IgG can penetrate into live human mononuclear cells (MNC) having receptors for the Fc portion of IgG. Because T cells with such receptors (Tgamma cells) seem to behave as suppressor cells in immune regulation and because this suppressor function is diminished in diseases where antinuclear antibodies appear, we considered the possibility that antinuclear IgG antibody could penetrate Tgamma cells and affect them. Herein we show that fluorescein-labeled anti-RNP IgG can penetrate into Tgamma cells, enriched by either mitogenic stimulation or separation with a subpopulation of T cells with low affinity for sheep erythrocytes. Incubation of MNC with anti-RNP IgG before carrying out the separation procedures resulted in apparent loss of Tgamma cells at the end of separation. To confirm that deletion had actually occurred, we performed a cytotoxicity assay using 51Cr-labeled T cells. Anti-RNP IgG had a significantly higher cytotoxic effect that normal IgG on T cells, particularly on those with low affinity for sheep erythrocytes that include most Tgamma cells. Suppressor cell function studied in a system where it was expanded, by either 7-day culture or incubation with concanavalin A, and detected in a reverse plaque-forming cell assay with rabbit anti-human immunoglobulin-developing antibody was found to be abrogated by the addition of anti-RNP IgG to the suppressor function-expanding cultures. Controls in Ig-free medium, or medium supplemented with normal human IgG, aggregated normal human IgG, BSA-anti-BSA immune complexes, or F(ab')2 fragments of the anti-RNP IgG, did not abrogate suppressor cell function. This indicates that the abrogation of suppressor cell function by anti-RNP IgG is due to its penetration into Tgamma cells. Suppressor cell loss and/or dysfunction caused by penetration of antinuclear antibodies into Tgamma cells may lead to the self-perpetuation of autoimmune disease.
D000818:Animals; D000906:Antibodies; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic; D005455:Fluorescent Antibody Technique; D006801:Humans; D007074:Immunoglobulin G; D007165:Immunosuppression Therapy; D008212:Lymphocyte Depletion; D009698:Nucleoproteins / Q000276:immunology*; D011817:Rabbits; D012261:Ribonucleoproteins / Q000276:immunology*; D012397:Rosette Formation; D013601:T-Lymphocytes / Q000276:immunology*
D000906:Antibodies; D007074:Immunoglobulin G; D009698:Nucleoproteins; D012261:Ribonucleoproteins