Activation-induced expression of cell surface CD28 on mouse T lymphocytes is inhibited by cyclosporine A

T-cell activation requires both T-cell receptor signaling and a costimulatory signal provided by CD28 which enhances and prolongs interleukin-2 (IL-2) production. To determine the effect of cyclosporine A (CsA) on constitutive and activation-induced CD28 expression, mouse T cells were exposed to CsA (0.1 mum) in the absence or presence of anti-CD3 monoclonal antibody (mAb). CD28 expression was then determined by flow cytometry. CsA treatment prevented activation-induced CD28 expression but did not affect constitutive CD28 expression. Inhibition of inducible CD28 expression by CsA was not rapidly reversible, requiring 48 h of restimulation in the absence of CsA for CD28 expression to return to control levels. T cells activated in the presence of combined anti-IL-2 and anti-CD25 mAb (both 10 mug/mL) also exhibited reduced CD28 expression, suggesting that activation-induced CD28 expression is, at least in part, an IL-2-dependent process. However, the inhibitory effect of CsA on activation-induced CD28 expression was maintained in the presence of exogenous IL-2 (250 U/mL). We conclude that CsA, by inhibiting activation-induced expression of costimulatory CD28 molecules by T lymphocytes, may interfere with the ability of CD28 to provide an optimal costimulatory signal for sustained IL-2 production following T-cell activation.