ROLE OF NONMAJOR HISTOCOMPATIBILITY COMPLEX ANTIGENS IN THE REJECTIONOF TRANSPLANTED MYOBLASTS

Myoblasts obtained from donors histoincompatible for several non-major histocompatibility complex antigens (i.e., including minor histocompa tibility antigens) and from syngeneic donors were transplanted without any immunosuppression into the muscles of male dystrophic C57BL/10J m dx/mdx mice. Myoblasts from syngeneic mice resulted in the formation o f a high percentage of dystrophin-positive fibers 16 weeks after the t ransplantation. There was no evidence of a cellular immune reaction ag ainst the donor myoblasts, i.e., no infiltration by CD4 or CD8 lymphoc ytes and no increased expression of granzyme B and interferon-gamma mR NAs. Transplantation of myoblasts obtained from donors histoincompatib le only for non- major histocompatibility complex antigens produced a transient increase of dystrophin-positive fibers at 4 weeks after tran splantation for some donor strains but not for others. For donor strai ns that did produce an increase at 4 weeks, the number of dystrophin-p ositive fibers was reduced 16 weeks after the transplantation. There w as evidence of a cellular immune reaction-infiltration by CD4 and by C DS lymphocytes and increased expression of granzyme B and interferon-g amma mRNAs. Transplantation of myoblasts obtained from male C57BL/10J +/+ mice into female C57BL/10J mdx/mdx mice also led to the presence o f only a few dystrophin-positive fibers with the same signs of cellula r immune reaction. In this later case, the cellular immune response wa s attributed to the H-Y minor antigens. Finally, antibodies against fe tal calf serum were detected after both syngeneic and nonsyngeneic tra nsplantations, indicating that the culture medium may also be a source of antigens. In mice, the presence of these antibodies against cultur e medium did not reduce the success of a first syngeneic transplantati on.