Effect of cyclosporine on the response of normal human lymphocytes to cytomegalovirus in vitro

Lymphocytes from healthy volunteers seropositive for cytomegalovirus (CMV) demonstrated strong lymphoproliferative responses to CMV-infected and glutaraldehyde-fixed foreskin fibroblasts (CMVFF(x)) when cocultured for 6 days. Addition of the immunosuppressive drug cyclosporine (CsA) to the cultures resulted in a 10-fold reduction (P < 0.001) in counts per minute of [³H]thymidine uptake. The proliferative response to noninfected fixed fibroblasts was also reduced 10-fold. Kinetic studies showed an inhibition of the lymphoproliferative response and not an alteration in the time course kinetics in CsA-treated cultures. Cytotoxicity to CMV-infected and unfixed fibroblasts by lymphocytes primed by CMVFF(x) in the presence of 0.5 μg of CsA per ml was significantly reduced (P < 0.01) as compared with untreated cultures but remained significantly above background level (P < 0.01). The cytotoxic response was still present but reduced at concentrations of ≥ 1.0 μg/ml. Cytotoxicity to noninfected fibroblasts by CMVFF(x)-primed lymphocytes could be eliminated by as little as 0.5 μg of CsA per ml. Stimulation of lymphocytes by CMVFF(x) but not by noninfected fixed fibroblasts resulted in the in vitro generation of suppressor cells. CsA at a final concentration of 1.0 or 2.5 μg/ml did not significantly impair the induction of cells capable of suppressing the lymphoproliferative response of fresh autologous mononuclear cells to CMVFF(x). The findings described above may have important clinical implications in that a degree of protective immunity to CMV-infected cells is maintained even in the presence of CsA.