MHC class II-disparate heart but not skin allografts accelerate recipient cardiovascular disease (TRAN1P.934)

Abstract Organ transplantation is the most effective therapy for patients with end-stage organ failure but is limited by premature deaths from cardiovascular disease (CVD). The underlying mechanism is poorly understood. Using the ApoE-/- mouse model of atherosclerosis we investigated the effect of allograft rejection on recipient CVD by transplanting MHC class II-disparate cardiac or skin allografts from BM12 donor mice into C57BL/6 (B6) ApoE-/- recipient mice. Isografts from B6 donor mice were used as controls. Mice were observed for 12 weeks post transplantation. Allograft rejection of the BM12 hearts occurred around 60 days whereas the skin allografts were rejected within 15 days. About half of the mice with cardiac allografts died before 12 weeks although all mice with the skin grafts or heart isografts survived. The mice of heart allografts exhibited impaired cardiac function (decreased fractional shortening and enlarged left ventricles) and larger atherosclerotic lesions compared with those of cardiac isografts or skin grafts. CD4 T cells from blood and atherosclerotic lesions expressed higher levels of the early activation marker CD69 in hosts of heart allografts but not in those of isografts or skin allografts. Only the mice with cardiac allografts showed elevated mRNA levels for IFN-γ and IL-12a in their native hearts. Our data indicate that chronic allorecognition by alloreactive CD4 T cells elicits sustained inflammation and plays a key role in promoting recipient CVD.