Graft-Derived IL-6 Amplifies Proliferation and Survival of Effector T Cells That Drive Alloimmune-Mediated Vascular Rejection.

Background: IL-6 is an inflammatory cytokine that controls effector T cell responses but the mechanisms by which it controls allogeneic immune responses and vascular rejection that leads to transplant arteriosclerosis (TA) are poorly understood.

Methods: We have examined the mechanism by which IL-6 contributes to the pathogenesis of vascular rejection and TA using a murine aortic interposition model of vascular rejection.

Results: The absence of IL-6 production from artery graft cells reduced the development of vascular rejection and arteriosclerotic thickening.

Bim regulates alloimmune-mediated vascular injury through effects on T-cell activation and death.

Objective: Bim is a proapoptotic Bcl-2 protein known to downregulate immune responses and to also be required for antigen-induced T-cell activation. However, it is not known how the effect of Bim on these offsetting processes determines the outcome of allogeneic immune responses. We have defined the role of Bim in regulating alloantigen-driven T-cell responses in a model of vascular rejection.