[Frontiers in Bioscience 8, s838-844, September 1, 2003]

CHRONIC REJECTION: FAILURE OF IMMUNE REGULATION

Jeremy Goodman 1 and Thalachallour Mohanakumar 1,2

1 Departments of Surgery, 2 Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Definition of chronic rejection
3.1. Chronic renal rejection
3.2. Chronic hepatic rejection
3.3. Chronic cardiac rejection
3.4. Chronic pulmonary rejection
4. Immune mechanisms of chronic rejection
4.1. Humoral immunity
4.1.1. Anti-HLA antibodies
4.1.2. Non-HLA antibodies
4.2. Cellular immunity
4.2.1. Direct antigen presentation and CD8+ T cells
4.2.2. Indirect antigen presentation
4.2.3. Regulatory T cells
4.3. Soluble mediators
5. Summary and perspective
6. Acknowledgement
7. References

1. ABSTRACT

Current strategies for immunosuppression following organ transplantation focus on the prevention of acute rejection. As new generations of immunosuppressants have been developed, acute rejection rates have diminished markedly. The new challenge, then, is to prevent the devastating complications of chronic rejection, which have remained largely unchanged over the decades. The process of chronic rejection is a complex one, and it is likely that most, if not all, components of the immune system play some role in the long-term, smoldering failure of organs following transplantation. Through a better understanding of their individual contributions as well as interactions, new strategies may be developed to overcome this problem. We present here an overview of the major immune components thought to be involved in chronic rejection.