Sliced male C57BI/10Sn (H2-b) donor muscles were grafted into the female hi
stocompatible muscles of untreated, FK506-treated, and T-cell depleted (wit
h or without thymic tolerization) dystrophic (mdx; H2-b) and normal (C57BI/
10Sn; H2-b) hosts, and also into histoincompatible normal (Balb/c; H2-d) ho
sts. The fate of male donor nuclei was monitored on tissue sections by in s
itu hybridization with a Y-chromosome specific probe. The results demonstra
te that the dystrophic environment is more conducive than normal muscle to
donor myoblast migration, with the distance moved being threefold greater a
t 12 weeks in dystrophic hosts. T-cell depletion was significantly more eff
ective than FK506 treatment at enhancing donor myoblast emigration in both
histocompatible and histoincompatible hosts at 3 weeks. Furthermore, the ef
fects of T-cell depletion were sustained in histoincompatible hosts at 12 w
eeks. These data endorse the use of host T-cell depletion as a promising lo
ng-term strategy to improve myoblast transfer therapy (MTT) in the clinical
situation. (C) 2000 John Wiley & Sons, Inc.