Suppression of cytokine-dependent human T-cell proliferation by intravenous immunoglobulin.
Human intravenous immunoglobulin (hIVIG) modifies the course of numerous immune-mediated diseases, but its specific mode of action remains unknown. 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 antibody, tetanus toxoid antigen or the combination of a phorbol ester/ionomycin (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 anti-CD3 and tetanus but not P/I-induced proliferation in a dose-dependent manner. Addition of exogenous IL-2 to the cultures overcame the inhibitory effect of hIVIG; addition of IL-4 was ineffective. To further define the effect of hIVIG on specific cell populations, competent, purified T cells were stimulated with anti-CD3 or phorbol ester for three days in the presence of hIVIG. Addition of hIVIG blocked anti-CD3 and 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 significantly prevented the synthesis/secretion of both IL-2 and IL-4 in PDB-stimulated competent T cells. Taken together, these data suggest that one mechanism of action of hIVIG may be through its interference with cytokine-dependent T-cell proliferation.
Amran
D
D
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
Renz
H
H
Lack
G
G
Bradley
K
K
Gelfand
E W
EW
D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008934:Mitogens / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism
D016207:Cytokines; D016756:Immunoglobulins, Intravenous; D007376:Interleukin-2; D008934:Mitogens; D015847:Interleukin-4; D012313:RNA; D004247:DNA