Role of non-major histocompatibility complex antigens in the rejection of transplanted myoblasts

Myoblasts obtained from donors histoincompatible for several non-major histocompatibility complex antigens (i.e., including minor histocompatibility antigens) and from syngeneic donors were transplanted without any immunosuppression into the muscles of male dystrophic C57BL/10J mdx/mdx mice. Myoblasts from syngeneic mice resulted in the formation of a high percentage of dystrophin-positive fibers 16 weeks after the transplantation. There was no evidence of a cellular immune reaction against the donor myoblasts, i.e., no infiltration by CD4 or CD8 lymphocytes and no increased expression of granzyme B and interferon-gamma mRNAs. Transplantation of myoblasts obtained from donors histoincompatible only for non- major histocompatibility complex antigens produced a transient increase of dystrophin-positive fibers at 4 weeks after transplantation for some donor strains but not for others. For donor strains that did produce an increase at 4 weeks, the number of dystrophin-positive fibers was reduced 16 weeks after the transplantation. There was evidence of a cellular immune reaction-infiltration by CD4 and by CD8 lymphocytes and increased expression of granzyme B and interferon-gamma mRNAs. Transplantation of myoblasts obtained from male C57BL/10J +/+ mice into female C57BL/10J mdx/mdx mice also led to the presence of only a few dystrophin-positive fibers with the same signs of cellular immune reaction. In this later case, the cellular immune response was attributed to the H-Y minor antigens. Finally, antibodies against fetal calf serum were detected after both syngeneic and nonsyngeneic transplantations, indicating that the culture medium may also be a source of antigens. In mice, the presence of these antibodies against culture medium did not reduce the success of a first syngeneic transplantation.