title: Transient complement inhibition plus T-cell immunosuppression induces long-term survival of mouse-to-rat cardiac xenografts.
abstract: BACKGROUND
  The use of anti-B-cell and T-cell immunosuppressive agents leads to only a few weeks' survival of mouse-to-rat cardiac xenografts.
  
  
  METHODS
  BALB/c cardiac xenografts were transplanted to Lewis rats treated with cyclosporine (CsA) and/or cobra venom factor (CVF).
  
  
  RESULTS
  CsA alone did not prolong xenograft survival (2.2+/-0.4 days), whereas CVF alone led to minimal prolongation of survival (5.6+/-0.8 days) as compared with nontreated recipients (2.4+/-0.5 days). The combination of CsA plus CVF, the latter given for either 2 days or 11 days, resulted in long-term survival of 14/16 hearts (> 100 days). Production of IgM elicited xenoreactive antibodies (EXA) peaked on day 4 after transplantation and decreased thereafter. Production of IgG EXA occurred only in the control group, whereas, in the CsA/CVF-treated group, IgG EXA were totally suppressed. Long-term surviving grafts showed (i) excellent preservation of morphology and minimal leukocyte infiltration, (ii) deposition of IgM, IgG and weak C3 deposition on the graft endothelium, (iii) low level infiltration by rat macrophages, (iv) replacement of mouse dendritic cells by class II+ rat macrophages, and (v) expression within endothelial and smooth muscle cells, macrophages, and myocytes of HO-1, a "protective gene" not seen in the rejected hearts.
  
  
  CONCLUSIONS
  Our present findings suggest that long-term mouse-to-rat cardiac xenograft survival is induced by temporary suppression of C activation and sustained T-cell suppression leading to inhibition of IgG EXA production. Florid expression of a protective gene (HO-1) may contribute to survival.
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: N
authors.initials: N
authors.lastname: Koyamada
authors.forename: T
authors.initials: T
authors.lastname: Miyatake
authors.forename: D
authors.initials: D
authors.lastname: Candinas
authors.forename: W
authors.initials: W
authors.lastname: Mark
authors.forename: P
authors.initials: P
authors.lastname: Hechenleitner
authors.forename: W W
authors.initials: WW
authors.lastname: Hancock
authors.forename: M P
authors.initials: MP
authors.lastname: Soares
authors.forename: F H
authors.initials: FH
authors.lastname: Bach
mesh_terms: D000818:Animals; D000910:Antibodies, Heterophile / Q000032:analysis; D003169:Complement Inactivator Proteins / Q000494:pharmacology*; D006085:Graft Survival / Q000502:physiology*; D016027:Heart Transplantation; D007165:Immunosuppression Therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000502:physiology*; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000276:immunology
chemical_list: D000910:Antibodies, Heterophile; D003169:Complement Inactivator Proteins