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 immune competent animals has been limited by the fact that a cellular immune attack of the host against transduced muscle fibers prevented long-term transgene expression. In this study we treated adult dystrophic [mdx] mice with daily subcutaneous injections of the immunosuppressive drug FK506 (tacrolimus) over 10 and 30 days after adenovirus-mediated reporter gene transfer and compared the transduction level to saline-injected controls. After 30 days, transgene expression was no longer demonstrable 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-lymphocytes in the muscles of the immunosuppressed group compared to controls.
Lochmüller
H
H
Montreal Neurological Institute, McGill University, Quebec, Canada.
Petrof
B J
BJ
Allen
C
C
Prescott
S
S
Massie
B
B
Karpati
G
G
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015870:Gene Expression / Q000187:drug effects*; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D007165:Immunosuppression Therapy; D018655:Lymphocyte Count; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes; D016559:Tacrolimus / Q000494:pharmacology*; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D001616:beta-Galactosidase; D016559:Tacrolimus