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 cyclosporine treatments have been reported in the prevention of liver allograft rejection. On this basis, we examined the effect of FK506 on pathogenesis of cytomegalovirus (CMV) infection in mice. FK506 induced apparent immunosuppression in mice which could be monitored by the level of antibody production. The effective dose of trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH) for 50% reduction in antibody production was 0.9 mg/kg. Even in such an immunosuppressed status at this or higher dose of FK506, CMV infection was relatively alleviated, which was observed by the frequency of virus isolation and the mean virus titer of the lungs of mice treated with 0.1-1 mg/kg FK506 in comparison to untreated mice. The dose of FK506 attaining 50% frequency of lung infection was 1.5 mg/kg. The activity of natural killer (NK) cells was enhanced in infected mice. This enhancement was stronger in infected mice treated with FK506 at 0.32 mg/kg and 10 mg/kg than in untreated infected mice on day 3 post infection (p.i.). Thus, an immunosuppressant FK506 augmented inducible NK cell activity and alleviated MCMV infection even under immunosuppression.