D. Amran et al., SUPPRESSION OF CYTOKINE-DEPENDENT HUMAN T-CELL PROLIFERATION BY INTRAVENOUS IMMUNOGLOBULIN, Clinical immunology and immunopathology, 73(2), 1994, pp. 180-186
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.