Coronary arteriosclerosis after T-cell-mediated injury in transplanted XXXX hearts: role of @entity60 .

@entity455 @entity8022 @entity4288 @entity19 @entity1711 @entity60 @entity1961 @entity1710 @entity6580 @entity8024 @entity130
This study evaluated the contribution of acute parenchymal rejection and @entity60 to the development of @entity455 ( @entity455 ) in totally allogeneic @entity19 cardiac transplants. BALB/c ( @entity8022 ) hearts were transplanted into wild-type C57BL/6 (B6, H-2b) or B6 @entity60 -deficient (GKO) recipient @entity19 . Assessing the role of acute parenchymal rejection in the @entity455 process involved two different immunosuppression protocols using anti- @entity1961 and -CD8 monoclonal antibodies (MAbs): virtually complete long-term immunosuppression (denoted as complete immunosuppression) was achieved by administering both MAbs 6, 3, and 1 day before transplantation and weekly thereafter; in contradistinction, a single, early, transient episode of rejection (transient rejection) was attained by administering MAbs beginning 4 days after transplant and then at weekly intervals. The extent and duration of T cell depletion under these two regimens were evaluated using flow cytometric analysis of peripheral blood lymphocytes. After a single injection of MAbs, peripheral blood @entity1961 + and CD8+ T cell depletion was approximately 98% at 1 week and approximately 88% at 2 weeks. After three injections (analogous to days 6, 3, and 1 before transplant), peripheral blood @entity1961 + and CD8+ T cell depletion was >98% at 2 weeks and approximately 87% at 4 weeks. Functioning cardiac allografts were removed at 8 and 12 weeks after transplant and analyzed by @entity1710 and @entity1711 , elastic tissue, and immunohistochemical stains, and the severity of parenchymal rejection versus @entity455 was scored. With complete immunosuppression (antibody before and after transplant), BALB/c allografts showed little parenchymal rejection or @entity455 , suggesting that persistent depletion of T cells blocked subsequent development of @entity455 . However, even a single transient acute rejection episode allowed the subsequent development of @entity455 accompanied by augmented major histocompatibility complex (MHC) class II, @entity6580 , and @entity8024 expression at 12 weeks; these allografts showed no residual @entity1961 + or CD8+ T cells. In comparison, allografts undergoing transient rejection in GKO recipients did not develop @entity455 , despite persistent macrophage and natural killer cell (NK) infiltrates comparable to those seen in wild-type recipients. Moreover, the arterioles of hearts transplanted into GKO recipients showed no or minimal increases in MHC class II, @entity8024 , and @entity6580 relative to baseline expression. In conclusion, a single episode of @entity130 mediated by T cells suffices to evoke subsequent graft @entity4288 , even in the absence of additional T-cell-mediated injury, and the process appears to depend on @entity60 .
