A clinically relevant CTLA4-Ig-based regimen induces chimerism and tolerance to heart grafts.
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.
Li
S
S
Division of Cardiothoracic Surgery, University of Miami School of Medicine, Florida 33136, USA.
Thanikachalam
M
M
Pang
M
M
Kawaharada
N
N
Aitouche
A
A
Pham
S M
SM
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*
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