CD4+ T cell-depleted splenocytes in MDX Mice Post Weaning

Nakamura, A., J. Bassaganya-Riera, R. Grange, and M.E. Houston (2004) CD4⁺ T cell-depleted splenocytes in MDX Mice Post Weaning. The FASEB Journal 18(5): (Abstract #476.14).

Duchenne muscular dystrophy (DMD) is a lethal muscle wasting disease caused by mutations in the gene encoding the cytoskeletal protein dystrophin. The role of T cells in DMD pathophysiology is not yet clearly defined, particularly when and to what extent these cells are activated. DMD pathophysiology in mdx mice begins around the age of weaning, ~21-d. In this study, we examined the phenotypic changes occurring in the thymus and spleen of mdx mice at ages 21- and 35-d using flow cytometry. Analysis of thymocyte subsets revealed that the percentages of CD4+ and CD8+ thymocytes in wild-type and mdx mice were not different at both ages, suggesting the initial stages of DMD pathophysiology do not affect thymocyte development. Between 21- and 35-d, spleens obtained from both wild-type and mdx mice demonstrated increases in CD3+/CD4+ T cells (14.6- and 6.9-fold, respectively; p < 0.0001), and CD8-/CD4+ T cells (11.1- and 3.3-fold, respectively; p < 0.0001). There were no differences in these cells between genotypes at age 21-d; however, at age 35-d, lower percentages of CD3+/CD4+ T cells (8.2% vs. 16.8%, p < 0.0001) and CD8-/CD4+ T cells (8.1% vs. 16.2%, p < 0.0001) were detected in mdx vs. wild-type spleens. These results suggest that between 21- and 35-d, CD4+T cells undergo greater apoptosis of CD4+ T cells in mdx mice and/or that CD4+ T cells migrate and are incorporated into other tissues, especially skeletal muscle.