title: Treatment with anti-CD154 antibody and donor-specific transfusion prevents acute rejection of myoblast transplantation.
abstract: 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.
authors.affiliation: Unité de Recherche en Génétique Humaine, Centre de Recherche du CHUL, Université Laval, Québec, Canada, G1V 4G2.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Camirand
authors.forename: Nicolas J
authors.initials: NJ
authors.lastname: Caron
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Turgeon
authors.forename: Aldo A
authors.initials: AA
authors.lastname: Rossini
authors.forename: Jacques P
authors.initials: JP
authors.lastname: Tremblay
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D016189:Dystrophin; D012333:RNA, Messenger; D023201:CD40 Ligand; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases