AUGMENTATION OF NATURAL-KILLER-CELL ACTIVITY-INDUCED BY CYTOMEGALOVIRUS-INFECTION IN MICE TREATED WITH FK506

Comparable rates of patient and graft survival after FK506 and cyclosp orine treatments have been reported in the prevention of liver allogra ft rejection. On this basis, we examined the effect of FK506;on pathog enesis of cytomegalovirus (CMV) infection in mice. FK506 induced appar ent immunosuppression in mice which could be monitored by the level of antibody production. The effective dose of trinitrophenyl-keyhole lim pet hemocyanin (TNP-KLH) for 50% reduction in antibody production was 0.9 mg/kg. Even in such an immunosuppressed status at this or higher d ose of FK 506, CMV infection was relatively alleviated, which was obse rved by the frequency of virus isolation and the mean virus titer of t he lungs of mice treated with 0.1 - 1 mg/kg FK 506 in comparison to un treated mice. The dose of FK506 attaining 50% frequency of lung infect ion was 1.5 mg/kg. The activity of natural killer (NK) cells was enhan ced in infected mice. This enhancement was stronger in infected mice t reated with FK506 at 0.32 mg/kg and 10 mg/kg than in untreated infecte d mice on day 3 post infection (p.i.). Thus, an immunosuppressant FK50 6 augmented inducible NK cell activity and alleviated MCMV infection e ven under immunosuppression.