Graft vasculopathy and tolerance: does the balance of Th cells contribute to graft vasculopathy?

BACKGROUND

Cardiac allograft vasculopathy (CAV) is sometimes observed even though the allograft may survive indefinitely. In this study, we examined whether or not the preferential activation of Th2-type cells prevents the development of CAV.

METHODS

Hearts from C57BL/10 mice were transplanted heterotopically into the abdominal cavities of C3H.He recipient mice, and monoclonal antibodies (mAbs) to T-cell receptor (TCR) alphabeta or CD80/CD86 were administered after transplantation. The incidence of CAV was then examined histologically. To investigate the relative Th1/Th2 balance, the levels of IFNgamma and IL4 in the transplanted hearts were measured.

RESULTS

Indefinite heart graft survival was observed in mice treated with either the anti-TCRalphabeta or anti-CD80/CD86 mAbs and these mice accepted donor-type (C57BL/10) skin grafts but rejected those from a third party (BALB/c). Evidence of CAV was found in the mice treated with the anti-TCRalphabeta mAb, but CAV did not develop in the mice treated with anti-CD80/CD86 mAbs. Preferential activation of Th2-type cells was dominant in the tolerant mice treated with anti-TCRalphabeta mAb, but it was not dominant in the tolerant mice treated with anti-CD80/CD86 mAbs.

CONCLUSION

These findings suggest that the dominance of Th2-type cells does not prevent allograft vasculopathy.