Open AccessIMMUNOSUPPRESSION WITH MONOCLONAL ANTIBODIES AND CTLA4-Ig AFTER MYOBLAST TRANSPLANTATION IN MICE
Author(s) -
B. Guérette,
Marc Gingras,
Kathryn J. Wood,
Raynald Roy,
Jacques P. Tremblay
Publication year - 1996
Publication title -
transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.45
H-Index - 204
eISSN - 1534-6080
pISSN - 0041-1337
DOI - 10.1097/00007890-199610150-00015
Subject(s) - immunosuppression , monoclonal antibody , transplantation , antibody , immunology , medicine , monoclonal
Various combinations of monoclonal antibodies specific for lymphocyte cell surface antigens and a recombinant molecule (CTLA4-Ig) were used to immunosuppress mice after transplantation of MHC-incompatible myoblasts. To assess the effectiveness of the immunosuppression, the donor myoblasts were obtained from a transgenic mouse (TnI LacZ1/29) containing a beta-galactosidase (beta-gal) reporter gene under the control of a muscle-specific promoter. No muscle fibers expressing beta-gal were observed 1 month after the myoblast transplantation, when the animals were not immunosuppressed or were treated with CTLA4-Ig alone. Approximately 50% of the muscle fibers expressed the beta-gal reporter gene 1 month after transplantation in mice treated with CTLA4-Ig combined with an anti-CD4 monoclonal antibody and in mice treated with a combination of anti-CD4, anti-CD8, and anti-lymphocyte function-associated antigen-1. The percentage of beta-gal-labeled muscle fibers increased to 94% when this combination of the three monoclonal antibodies was administrated weekly for 3 weeks. Although excellent graft survival rates were obtained 1 month after transplantation, reflecting an effective immunosuppression by these three treatments, no beta-gal-positive fibers were found 2 months after the transplantation, indicating the inability of these immunosuppressive agents to maintain long-term graft survival and induce tolerance to the myoblasts and muscle fibers of donor origin.