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

Ann Thorac Surg. 2001 Oct;72(4):1306-10. doi: 10.1016/s0003-4975(01)03066-1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Animals
  • Antigens, CD
  • Antigens, Differentiation / pharmacology*
  • Antilymphocyte Serum / pharmacology
  • Bone Marrow Transplantation / immunology*
  • CTLA-4 Antigen
  • Graft Survival / immunology
  • Heart Transplantation / immunology*
  • Humans
  • Immunoconjugates*
  • Rats
  • Rats, Inbred ACI
  • Rats, Inbred WF
  • Skin Transplantation / immunology
  • Transplantation Chimera / immunology*
  • Transplantation Tolerance / immunology*

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • Antilymphocyte Serum
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ctla4 protein, rat
  • Immunoconjugates
  • Abatacept