LYMPHOCYTE INFILTRATION FOLLOWING ALLOMYOBLAST AND XENOMYOBLAST TRANSPLANTATION IN MDX MICE

Human and mouse (C57BL/10SnJ +/+) myoblasts were injected separately i n the muscles of C57BL/10ScSn mdx/mdx mice, Mouse myoblasts (C57BL/10S nJ +/+) were also injected in normal mice (C57BL/10SnJ+/+ and BALB/c+/ +). Some muscles that received a xenotransplantation (i.e., human myob lasts) were previously injected with a myotoxin, i,e., notexin. This t reatment was not used for the allografts (i,e., mouse myoblasts), Huma n myoblast injections did not increase the number of dystrophin-positi ve cells above the background level due to backmutation. Moreover, the human myoblasts detected with an anti-HLA antibody decreased rapidly during the 6-week followup, The injection of normal mouse myoblasts in mdx mice did, however, increase the number of dystrophin-positive fib ers. Moreover, numerous cells expressing mouse MHC class Il, macrophag es, granulocytes, neutrophils, natural killer cells, and a subset of T lymphocytes were detected by immunohistochemistry in cryostat section s of myoblast-injected muscles. These cells were present within 1 week of the myoblast injection in the muscle regions containing injected h uman or mouse myoblasts, and progressively decreased during the 6-week follow-up in the human myoblast transplantation. Lymphocyte infiltrat ion reached a significant level following xeno- and alloincompatible t ransplantations. Antibodies against the human myoblasts and against al loincompatible myoblasts were also detected in the serum of the recipi ents. These results suggest that humoral and cellular immune reactions are responsible for the poor outcome of myoblast transplantation in m ice and could be involved in failure of transplantation in Duchenne mu scular dystrophy patients. These results indicate that adequate immuno suppressionmust be used in these patients. (C) 1995 John Wiley and Son s, Inc.