Locally produced and activated complement as a mediator of alloreactive T cells

Immune-mediated rejection remains a significant obstacle preventing long term survival of transplanted organs. Emerging information derived from multiple groups has recently shown that the complement system, traditionally considered a central arm of innate immunity and a primary effector arm of antibody-mediated immunity, plays an additional key role as a regulator of adaptive alloreactive T cell immunity. Complement components produced by immune cells are activated locally and the resultant activation products guide the development of effector T cell immune responses. In the context of organ transplantation, manipulation of local complement activation influences the strength and effector functions of alloreactive T cells which are central mediators of immune mediated rejection. Further definition of the molecular basis underlying complement's effects on cellular alloimmunity has the potential to provide novel targets for the prevention and treatment of injury to solid organ transplants.