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Ann Thorac Surg 2001;72:1306-1310
© 2001 The Society of Thoracic Surgeons

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Original article: cardiovascular

A clinically relevant CTLA4-Ig-based regimen induces chimerism and tolerance to heart grafts

^a Division of Cardiothoracic Surgery, University of Miami School of Medicine, Miami, Florida, USA
^b Division of Cardiothoracic Surgery, Sapporo Medical University, Sapporo, Japan

Address reprint requests to Dr Pham, Division of Cardiothoracic Surgery, University of Miami School of Medicine, Highland Professional Building, 1801 N W 9th Ave, 5th Floor, Miami, FL 33136
e-mail: spham{at}med.miami.edu

Presented at the Thirty-seventh Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 29–31, 2001.

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 (10⁸ 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.

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