αβTCR + T cells play a nonredundant role in the rejection of heart allografts in mice

Abstract

Background: Although the transplantation of solid organs and cellular grafts is a clinical routine, the morbidity and mortality associated with immunosuppression is significant. This could be avoided by the induction of donor-specific tolerance. To develop targeted antirejection strategies and regimens to induce donor-specific tolerance, cell populations in the recipient-mediating rejection of solid organ and cellular grafts must be defined. In this study we examined the role of αβ-TCR + cells in the rejection of allogeneic heart grafts, by use of knockout (KO) mice deficient in the production of αβ-TCR + T cells. Methods: C57BL/6-Tcrb tmlMom (αβ-KO) and C57BL6/J (B6) recipient mice were transplanted with B10.BR/SgSnJ (B10.BR) or BALB/c heart allografts. Animals also received bone marrow from normal B10.BR donors, followed by donor-specific or third-party heart transplants. Results: Naive B6 control mice rejected B10.BR and BALB/c grafts within 16 days. In striking contrast, B10.BR and BALB/c heart allografts were indefinitely accepted in unmanipulated αβ-KO mice. The immune responsiveness was restored after bone marrow transplantation from normal donors. After bone marrow transplantation major histocompatibility–disparate BALB/c third-party heart grafts were rejected, whereas donor-specific grafts were still accepted. Conclusions: αβ-TCR + T cells play a nonredundant role in the rejection of heart allografts in mice. Bone marrow chimerism is associated with donor-specific transplantation tolerance. (Surgery 1999;126:121-6.)