alpha beta TCR+ T cells play a nonredundant role in the rejection of heartallografts in mice

Background. Although the transplantation of solid organs and cellular graft s is a clinical routine, the morbidity and mortality associated with immuno suppression is significant. This could be avoided by the induction of donor -specific tolerance. To develop targeted antirejection strategies and regim ens to induce donor-specific tolerance, cell populations in the recipient-m ediating rejection of solid organ and cellular grafts must be defined. In t his study we examined the role of alpha beta-TCR+ cells in the rejection of allogeneic heart grafts, by use of knockout (KO) mice deficient in the pro duction of alpha beta-TCR+ T cells. Methods. C57BL/6-Tcrb(tmlMom) (alpha beta-KO) C57BL6/J(B6) recipient mice w ere transplanted with B10.BR/SgSnJ (B10.BR) or BALB/c heart allografts. Ani mals also received bone marrow from normal B10.BR donors, followed by donor -specific or third-party heart transplants. Results. Naive BG control mice rejected B10.BR and BALB/c grafts within 16 days. In striking contrast, B10.BR and BALB/c heart allografts were indefin itely accepted in unmanipulated alpha beta-KO mire. The Immune responsivene ss was restored after bone marrow transplantation from normal donors. lifte r bone marrow transplantation major histocompatibility-disparate BALB/c thi rd-party heart grafts were rejected, whereas donor specific grafts were sti ll accepted. Conclusions: alpha beta-TCR+ T cells play a nonredundant role in the reject ion of heart allografts in mice. Bone marrow chimerism is associated with d onor specific transplantation tolerance.