REDUCTION OF DONOR-SPECIFIC CYTOTOXIC T-LYMPHOCYTE PRECURSORS IN PERIPHERAL-BLOOD OF ALLOGRAFTED HEART RECIPIENTS

Tolerance to allografted hearts in human recipients has been observed both in clinical situations and in in vitro experiments. To elucidate whether a quantitative change of alloreactive CTL is one of the mechan isms accounting for this graft tolerance, CTL precursor (CTLp) frequen cies in the peripheral blood of 10 heart recipients were measured agai nst spleen cells from donors and HLA nonidentical third-party persons. In this longitudinal follow-up study, we showed that the rejection re action(s) in the grafted heart correlated with CTLp frequencies in sam ples taken before transplantation against the donor spleen cells, but not with the CTLp frequencies against the spleen cells from the third- party persons. The CTLp frequencies against the spleen cells from dono rs decreased 4-6 months after transplantation, and remained at a low l evel afterward. However, the CTLp frequencies against spleen cells fro m third-party persons in blood samples obtained 1 year after transplan tation were not significantly different from those before transplantat ion. Therefore, we conclude that donor-reactive CTLs are important in rejecting allografted heart. The decrease in donor-specific CTLp after transplantation could explain the donor-specific tolerance. The decre ase may be due to homing of the specific CTLp to the graft, or by clon al deletion of the donor-reactive CTL caused by chronic alloantigen st imulation in the presence of immunosuppressive therapies.