The effects of FK-506 and cyclosporin A on the proliferation of PHA-stimulated T cells in response to IL-2, IL-4 or IL-6.

Stimulated by PHA, the T cells responded well to exogenous IL-2, IL-4 or IL-6, but the responses were inhibited by FK-506 or cyclosporin A (Cs A). In contrast, when stimulated by PMA, the T cells responded to IL-2 and IL-4, but not to IL-6 and the responses were not inhibited by FK-506 and Cs A. Kinetic studies showed that FK-506 and Cs A had no inhibitory effects on T cell proliferation in response to IL-2 and IL-4 after the resting T cells were pulsed with PHA alone for a certain time. However, the response of the PHA-pulsed T cells to IL-6 was still inhibited by FK-506 or Cs A, but the inhibitory effect gradually decreased as the time in which the PHA-pulsed T cells interacted with IL-6 was prolonged. In a control system, the proliferation of the T cells that were treated with FK-506 or Cs A for 3 h and washed 3 times was not inhibited when the T cells were stimulated with PHA in combination with either IL-2, IL-4 or IL-6. Our data suggest that FK-506 and Cs A interfere with the early steps of T cell proliferation after stimulation of PHA, but not PMA. It is likely that the two drugs inhibit the expression of lymphokine receptors, by interfering Ca(2+)-related signals and that IL-6 induces T cell proliferation in a different way than IL-2 and IL-4, which are FK-506- and Cs A-sensitive.