Effect of interferon-gamma, interleukin-2 and interleukin-4 on cyclosporin-A-mediated inhibition of anti-CD3-induced T-lymphocyte proliferation.
It is generally believed that cyclosporin A (CsA) inhibits T-cell activation largely by blocking interleukin (IL)-2 production, although CsA also inhibits the secretion of other growth-promoting lymphokines. To investigate the importance of downregulated synthesis of IL-4 and interferon (IFN)-gamma, in addition to IL-2, in CsA-mediated inhibition of T-lymphocyte proliferation, exogenous IL-2, IL-4, and IFN-gamma were added to murine T-cells stimulated with anti-CD3 monoclonal antibody in the presence of an inhibitory concentration of CsA. Either IL-2 or IL-4 alone were able to partially counteract the inhibitory effect of CsA on anti-CD3-induced T-lymphocyte proliferation, whereas IFN-gamma had no discernable effect. IL-2 and IL-4, in combination, were able to largely reverse the immunosuppressive activity of CsA. These results indicate that (1) CsA fails to block T-cell signal transduction pathways coupled to IL-2 and IL-4 receptors, and (2) IL-2 and IL-4 have an additive effect in promoting the proliferation of a heterogenous T-cell population stimulated with anti-CD3 monoclonal antibody.
Fitzpatrick
L
L
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Kaiser
M
M
Stewart
B H
BH
Hoskin
D W
DW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D007202:Indicators and Reagents; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007202:Indicators and Reagents; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma; D016572:Cyclosporine