L. Fitzpatrick et al., EFFECT OF INTERFERON-GAMMA, INTERLEUKIN-2 AND INTERLEUKIN-4 ON CYCLOSPORINE-A-MEDIATED INHIBITION OF ANTI-CD3-INDUCED T-LYMPHOCYTE PROLIFERATION, International journal of immunopharmacology, 16(4), 1994, pp. 289-293
It is generally believed that cyclosporin A (CsA) inhibits T-cell acti
vation 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 int
erferon (IFN)-gamma, in addition to IL-2, in CsA-mediated inhibition o
f 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 pathwa
ys coupled to IL-2 and IL-4 receptors, and (2) IL-2 and IL-4 have an a
dditive effect in promoting the proliferation of a heterogenous T-cell
population stimulated with anti-CD3 monoclonal antibody.