title: A clinically relevant CTLA4-Ig-based regimen induces chimerism and tolerance to heart grafts.
abstract: BACKGROUND
  We determined whether a nontoxic CTLA4-Ig-based conditioning regimen effected mixed chimerism and donor-specific tolerance when heart and bone marrow were transplanted simultaneously.
  
  
  METHODS
  Fully mismatched rat strain combinations were used. Recipients received total-body irradiation (300 centigrays), bone marrow (10(8) cells), and cardiac transplants from the donor on day 0. Subsequently, recipient animals received CTLA4-Ig (2 mg/kg, every other day, x 5 doses), tacrolimus (1 mg/kg/day; days 0 to 9), and one dose (10 mg) of antilymphocyte serum on day 10.
  
  
  RESULTS
  All bone marrow recipients (n = 7) developed mixed chimerism (mean = 25% +/- 9% at 1 year) and accepted cardiac allografts permanently (> 375 +/- 32 days). Recipients that received conditioning regimen but no bone marrow (n = 5) rejected donor hearts within 51 +/- 13 days (p < 0.01). Recipients that accepted heart grafts also permanently accepted (> 180 days) donor-specific skin grafts, but rapidly rejected (< 10 days) third-party skin grafts.
  
  
  CONCLUSIONS
  A nontoxic CTLA4-Ig-based conditioning regimen effects mixed chimerism and donor-specific tolerance when heart and bone marrow are transplanted simultaneously. This regimen may have clinical application.
authors.affiliation: Division of Cardiothoracic Surgery, University of Miami School of Medicine, Florida 33136, USA.
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: M
authors.initials: M
authors.lastname: Thanikachalam
authors.forename: M
authors.initials: M
authors.lastname: Pang
authors.forename: N
authors.initials: N
authors.lastname: Kawaharada
authors.forename: A
authors.initials: A
authors.lastname: Aitouche
authors.forename: S M
authors.initials: SM
authors.lastname: Pham
mesh_terms: D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000494:pharmacology*; D000961:Antilymphocyte Serum / Q000494:pharmacology; D016026:Bone Marrow Transplantation / Q000276:immunology*; D060908:CTLA-4 Antigen; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D018796:Immunoconjugates; D051381:Rats; D011912:Rats, Inbred ACI; D011920:Rats, Inbred WF; D016038:Skin Transplantation / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D000961:Antilymphocyte Serum; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556708:Ctla4 protein, rat; D018796:Immunoconjugates; D000069594:Abatacept