SUPPRESSION OF CYTOKINE-DEPENDENT HUMAN T-CELL PROLIFERATION BY INTRAVENOUS IMMUNOGLOBULIN

Human intravenous immunoglobulin (hIVIG) modifies the course of numero us immune-mediated diseases, but its specific mode of action remains u nknown. In order to delineate possible immunoregulatory mechanisms, we studied the effects of hIVIG on the in vitro proliferation of human T cells. Cells from normal donors were stimulated with anti-CD3 antibod y, tetanus toroid antigen or the combination of a phorbol ester/ionomy cin (P/I) and incubated with increasing concentrations of hIVIG (1 mg/ ml to 10 mg/ml) for three to seven days. Addition of hIVIG inhibited a nti-CD3 and tetanus but not P/I-induced proliferation in a dose-depend ent manner. Addition of exogenous IL-2 to the cultures overcame the in hibitory effect of hIVIG; addition of IL-4 was ineffective. To further define the effect of hIVIG on specific cell populations, competent, p urified T cells were stimulated with anti-CD3 or phorbol ester for thr ee days in the presence of hIVIG. Addition of hIVIG blocked anti-CD3 a nd phorbol ester-induced stimulation of competent T cells. In cultures of competent T cells, either IL-2 or IL-4 was successful in reversing the hIVIG-induced inhibition. In these cultures, hIVIG also significa ntly prevented the synthesis/secretion of both IL-2 and IL-4 in PDB-st imulated competent T cells. Taken together, these data suggest that on e mechanism of action of hIVIG may be through its interference with cy tokine-dependent T-cell proliferation. (C) 1994 Academic Press, Inc.