Treatment with anti-CD154 antibody and donor-specific transfusion prevents acute rejection of myoblast transplantation.
BACKGROUND
Achieving immunological tolerance to transplanted myoblasts would reduce the adverse effects associated with the sustained immunosuppression required for this experimental therapeutic approach in Duchenne muscular dystrophic patients.


METHODS
Mdx mice were transplanted with fully allogeneic BALB/c myoblasts in the tibialis anterior muscles. Seven days before transplantation (-7), host mice received 107 total donor spleen cells i.v. (donor-specific transfusion, DST) with 500 microg of anti-CD154 mAb i.p. on days -7, -4, 0, +4.


RESULTS
Results showed a high level of dystrophin expression in 83, 60, and 20% of the mice 1, 3, and 6 months, respectively, after transplantation of myoblasts. No antibodies against the donor cells were produced up to 3 months after transplantation. However, abundant activated cytotoxic cells were present in muscles still expressing high percentage of dystrophin positive fibers.


CONCLUSIONS
In conclusion, the DST + anti-CD154 mAb treatments effectively prolonged myoblast survival, but this treatment could not develop tolerance to complete allogeneic myoblast transplantation.
Camirand
Geoffrey
G
Unité de Recherche en Génétique Humaine, Centre de Recherche du CHUL, Université Laval, Québec, Canada, G1V 4G2.
Caron
Nicolas J
NJ
Turgeon
Nicole A
NA
Rossini
Aldo A
AA
Tremblay
Jacques P
JP
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001803:Blood Transfusion; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D023201:CD40 Ligand / Q000276:immunology* / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D017690:Cell Transplantation; D016207:Cytokines / Q000235:genetics; D016189:Dystrophin / Q000032:analysis; D006084:Graft Rejection / Q000517:prevention & control*; D053804:Granzymes; D051379:Mice; D008807:Mice, Inbred BALB C; D009132:Muscles / Q000737:chemistry / Q000166:cytology*; D009136:Muscular Dystrophies / Q000378:metabolism / Q000628:therapy*; D012333:RNA, Messenger / Q000032:analysis; D012697:Serine Endopeptidases / Q000235:genetics
D000911:Antibodies, Monoclonal; D016207:Cytokines; D016189:Dystrophin; D012333:RNA, Messenger; D023201:CD40 Ligand; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases