Abstract 579: Graft-Derived IL-6 Amplifies Proliferation and Survival of Effector T Cells that Drive Alloimmune-Mediated Vascular Rejection

Objective: IL-6 is an inflammatory cytokine that controls the development of effector T cell responses but the mechanisms by which it controls allogeneic immune responses and vascular rejection that leads to transplant arteriosclerosis (TA) is poorly understood. We have examined the effect of graft-derived IL-6. Methods: An aortic interposition model of vascular rejection and TA was performed using IL-6+/+ and IL-6-/- donors. Findings: The absence of IL-6 production from artery graft cells reduced the development of vascular rejection and arteriosclerotic thickening. There was no apparent effect of donor-derived IL-6 on endothelial cell integrity or on the intimal accumulation of smooth muscle cells and macrophages. However, reduced vascular pathology in IL-6-/- artery grafts was accompanied by a significant reduction in the accumulation of CD4 and CD8 T cells. Further, the absence of graft-derived IL-6 resulted in a significant decrease in the activation and proliferation of alloreactive CD4 and CD8 T ce...