[Frontiers in Bioscience 14, 3771-3781, January 1, 2009]

Dysregulation of CD8+ lymphocyte apoptosis, chronic disease, and immune regulation

Karen L. Wood1, Homer L. Twigg III2, Andrea I. Doseff1,3

1Department of Medicine, The Ohio State University Medical Center, Columbus, OH, USA, 2Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA, 3Department of Molecular Genetics, The Ohio State University Medical Center, Columbus, OH, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Normal lymphocyte lifespan
4. Expansion of CD8+CD57+ lymphocytes
5. Function of CD57+
6. Links to autoimmunity / immune deficiency / and immune suppression
6.1. Intrinsic regulatory properties
6.2. Formation of autoimmunity from an ineffective CTL pool
6.3. Increased susceptibility to infection
7. Alteration in apoptosis
8. Conclusions
9. Acknowledgements
10. References

1. ABSTRACT

Expansion of CD8+ lymphocyte subsets are found in many states with chronic antigenic exposure including HIV, multiple myeloma, rheumatoid arthritis, CMV infection, transplantation and even normal aging. These expansions are characterized by the expression of CD57 antigen and the loss of CD28-. These lymphocytes are thought to represent clonally expanded cytotoxic T lymphocytes (CTL) that have become senescent and lack proliferative ability. These cells also demonstrate suppressive properties and have been linked with immunodeficiency raising the question of the function of these cells in relationship to immunoregulation. Alterations in the CD95/Fas apoptotic pathway and changes in pro-survival factors such as Hsp27 likely contribute to this lymphocyte subset expansion. Further understanding of the normal CD8+ lymphocyte response to antigen and the factors that lead to abnormal continued expansion in certain disease states will be crucial to understanding the pathogenesis of chronic antigenic stimulation.