IMMUNOSUPPRESSION BY FK506 MARKEDLY PROLONGS EXPRESSION OF ADENOVIRUS-DELIVERED TRANSGENE IN SKELETAL-MUSCLES OF ADULT DYSTROPHIC-[MDX] MICE

Adenovirus-mediated gene transfer into skeletal muscles of adult immun e competent animals has been limited by the fact that a cellular immun e attack of the host against transduced muscle fibers prevented long-t erm transgene expression. In this study we treated adult dystrophic [m dx] mice with daily subcutaneous injections of the immunsuppressive dr ug FK506 (tacrolimus) over 10 and 30 days after adenovirus-mediated re porter gene transfer and compared the transduction level to saline-inj ected controls. After 30 days, transgene expression was no longer demo nstrable in the control group, whereas it remained at about 70% of the 10-day transduction value in the FK506 treated group. In addition, we demonstrated a reduction in the number of CD3 and CD8 positive T-lymp hocytes in the muscles of the immunosuppressed group compared to contr ols. (C) 1995 Academic Press Inc.