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(American Journal of Pathology. 2005;166:1701-1710.)
© 2005 American Society for Investigative Pathology

Effects of T-Lymphocyte Depletion on Muscle Fibrosis in the mdx Mouse

Jamie Morrison*, Donald B. Palmer{dagger}, Stephen Cobbold{ddagger}, Terence Partridge* and George Bou-Gharios§

From Muscle Cell Biology,* Clinical Sciences Centre, and the Department of Medicine,§ Imperial College School of Medicine, Hammersmith Hospital, London; the Department of Veterinary Basic Sciences,{dagger} Royal Veterinary College, London; and the Sir William Dunn School of Pathology,{ddagger} University of Oxford, Oxford, United Kingdom

Duchenne muscular dystrophy was initially described as a myosclerosis because of the conspicuous progression of interstitial fibrosis. Using the mdx mouse homologue, we have shown previously that the accumulation of intramuscular collagen is profoundly influenced by the presence or absence of T lymphocytes. Here we have used thymectomy and antibody depletion to examine the effect of ablating CD4 or CD8 or both subsets of T lymphocytes on skeletal muscle fibrosis in mdx and C57BL10 (wild-type) mice. Depletion of either or both subsets at 4 weeks of age did not influence fibrosis in mdx mice, as determined by measuring hydroxyproline levels and collagen deposition in diaphragm. Additionally, expression of transforming growth factor-ß1, which is implicated in collagen deposition, either decreased (mdx mice) or increased (C57BL/10 mice) after double CD4/8 depletion. Our data suggest that depletion of lymphoid cells may affect the tight regulatory control of transforming growth factor-ß1, with possible pleiotropic effects, and more importantly, that the fibrotic process is self-sustaining from a very early stage.




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