CONTENTS

Introduction................................................................................................................................... 253

Autologous Cell-Mediated Killing via Intercellular Contacts.....................................................

MonocyteZMacrophage-Mediated T Cell Apoptosis............................................................. 254

CD4+ T Cell Apoptosis.......................................................................................................... 254

CD8+ T Cell Apoptosis.......................................................................................................... 257

Dendritic Cell-Mediated T Cell Apoptosis............................................................................ 258

T Cell-Mediated Apoptosis.................................................................................................... 258

Autologous Cell-Mediated Killing via the Release of Soluble Factors...................................... 259

Cytotoxic HIV Proteins.......................................................................................................... 259

Env.......................................................................................................................................... 259

Nef, Tat, Vpr........................................................................................................................... 260

Cytotoxic Factors................................................................................................................... 260

Autologous Cell-Mediated Killing Results in Immune Suppression........................................... 260

Immune Suppression.............................................................................................................. 260

Reservoirs............................................................................................................................... 261

Conclusion.....................................................................................................................................

Acknowledgments......................................................................................................................... 262

References..................................................................................................................................... 263

INTRODUCTION

Human immunodeficiency virus type 1 (HIV-1) infection causes functional impairment and pro­gressive loss of T lymphocytes, leading to immunodeficiency and AIDS. Direct lysis of infected T lymphocytes and apoptosis or programmed cell death of bystander cells occur during HIV-1 replication in vitro. The relative importance of direct cytopathic effects compared with apoptosis of uninfected bystander cells remains a subject of controversy. Most of the apoptotic T lymphocytes in the peripheral blood and lymphoid tissues of HIV-infected subjects are uninfected. Increased apoptosis of other types of uninfected cells, B cells, thymocytes, and neurons is also detected in HIV-infected subjects. Among mechanisms that are involved in HIV-associated apoptosis of bystander cells are the death of bystander cells by proapoptotic virus proteins or cytotoxic factors that are released by infected cells, and altered expression of cellular apoptosis regulatory molecules by lymphocytes and antigen-presenting cells (APC) as a consequence of HIV-mediated immune activation. Macrophages (M0), dendritic cells (DCs), CD4⁺ T cells, and CD8⁺ T cells derived from HIV-infected patients may induce the death of uninfected T lymphocytes, indicating that apoptosis of uninfected bystander cells plays an important role in AIDS pathogenesis.