[Frontiers in Bioscience 14, 4386-4400, January 1, 2009]

Death of effector memory T cells characterizes AIDS

Laforge Mireille2, Senik Anna2, Cumont Marie-Christine1, Monceaux Valerie1, Hurtrel Bruno1, Estaquier Jerome1,2,3

1CNRS URA 1930, Unite de Physiopathologie des Infections Lentivirales, Institut Pasteur, 28 rue du Docteur Roux, Paris, France, 2 INSERM U 841, Creteil, Paris, France, 3AP-HP, Hopital Henri Mondor, Creteil, France

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. The level of apoptosis predicts further progression to AIDS
4. Effector memory T cell subpopulation expressing CCR5 is the main population prone to die by apoptosis
5. Productive HIV-1 infection mediates CD4 T cell death
6. Exposure to HIV viral particles primes memory CD4 T cells for apoptosis
7. Cytokines regulate memory CD4 T cell apoptosis
8. Death of memory CD4 T cells is associated with mitochondrial permeabilization
9. Acknowledgements
10. References

1. ABSTRACT

The adaptive effector CD4+ T helper-mediated immune response is highly heterogeneous, based on the development of distinct subsets that are characterized by the expression of different profiles of cell surface markers. Functional impairment of T cells is characteristic of many chronic mouse and human viral infections. Excessive induction of apoptosis in infected and uninfected CD4+ T cells has been proposed as one of the pathogenic mechanisms that may impair the immune response and cause the development of acquired immune deficiency syndrome (AIDS). Thus, the death of effector/memory CD4+ T cells during both the acute and chronic phase represents one the main characteristic of such viral infection that predicts disease outcome. Improving our understanding of the molecular mechanisms leading to the death of memory CD4+ T cells should enable us to improve vaccination protocols and treatments, by combining them with antiretroviral drugs and molecules designed to decrease apoptotic phenomena.