[Frontiers in Bioscience S1, 117-124, June 1, 2009]

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

Peter N. Lalli1, Wuding Zhou2, Steven Sacks2, M. Edward Medof1, Peter. S. Heeger3

1Institute of Pathology, Case Western Reserve University, Cleveland OH 44106 USA, 2MRC Centre for Transplantation, King's College London, UK, 3Dept of Medicine, Mt Sinai School of Medicine, NY, NY 10025 USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Overview of the complement cascade
4. The role of complement in transplant rejection
4.1. Complement contributing to the inflammatory response
4.2. Complement modulating allospecific T cell responses
5. Implications for therapy
6. Conclusions
7. Acknowledgement
8. References

1. ABSTRACT

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.