Cell Activation and Apoptosis in HIV Infection: Implications for Pathogenesis and Therapy

245 Pages·1995·7.045 MB·English

by  Jeffrey Laurence (auth.), Jean-Marie Andrieu, Wei Lu (eds.)

CELL ACTIVATION AND
APOPTOSIS IN
HIV INFECTION
Implications for Pathogenesis and Therapy
ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
Editorial Board:
NATHAN BACK, State University of New York at Buffalo
IRUN R. COHEN, The Weizmann Institute of Science
DAVID KRITCHEVSKY, Wistar Institute
ABEL LAJTHA, N. S. Kline Institute for Psychiatric Research
RODOLFO PAOLETTI, University of Milan
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CELL ACTIVATION AND
APOPTOSIS IN
HIV INFECTION
Implications for Pathogenesis and Therapy
Edited by
Jean-Marie Andrieu
Wei Lu
Laennec Hospital
Paris, France
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
Librar y of Congress Catalog1ng-in-PublicatIo n Data
Cell activatio n and apoptosi s i n HIV infectio n : implication s fo r
pathogenesis and therap y / edite d by Jean-Marie Andrieu and Wei Lu.
p. cm. — (Advances i n experimental medicine and biolog y ; v.
374)
Proceedings of th e Firs t Internationa l Symposium on Cellula r
Aproaches t o th e Control of HIV Disease, held Jul y 11-12, 1994, i n
Paris, France—T.p. verso.
Includes bibliographica l reference s and index.
ISBN 978-1-4613-5823-7 ISBN 978-1-4615-1995-9 (eBook)
DOI 10.1007/978-1-4615-1995-9
1. HIV infections—Pathophysiology—Congresses . 2. Apoptosis-
-Congresses. 3. Lymphocyte transformation—Congresses .
I. Andrieu, Jean-Marie. II .L u, Wei. III . Internationa l Symposium
on Cellula r Approaches t o th e Control of HIV Disease (1s t 1994 :
Paris, France) IV. Series .
[DNLM: 1. HIV Infections—immunology—congresses . 2. HIV
Infections—therapy—congresses . 3. HIV Infections—immunology -
-congresses. 4. Apoptosis—immunology—congresses. 5. T
-Lymphocytes— immunology—congresses. W1 AD559 v.374 1995 / WC
503 C393 1995]
QR201.A37C54 1995
616.97'92—dc20
DNLM/DCL
for Librar y of Congress 95-17728
CIP
Proceedings of the First International Symposium on Cellular Approaches to the Control of HIV Dis
held July 11-12, 1994, in Paris, France
ISBN 978-1-4613-5823-7
© 1995 Springer Science+Business Media New York
Originally published by Plenum Press, New York in 1995
Softcover reprint of the hardcover 1st edition 1995
10 9 8 7 6 5 4 3 2 1
All rights reserved
No part of this book may be reproduce,d stored in a retrieval system, or transmitted in any form or b
means, electronic, mechanica, lphotocopying, microfilming, recording, or otherwise, without writte1
permission from the Publisher
PREFACE
In the past decade, the global efforts in the control of HIV disease were basically
concentrated on the search for anti-retroviral agents. So far, anti-HIV therapies have been
shown to be disappointing because of rapid development of drug-resistant mutant variants.
Despite this drawback in the therapeutic fight against HIV infection, antiviral research
should be actively pursued.
However, failure of antiviral therapy indicates that other avenues of research should
be rapidly explored with the same energy. In this setting, striking advances have been
recently made in the dissection and understanding of the viro-immunological processes
governing the progressive destruction of lymphoid organs associated with AIDS develop
ment, and HIV-induced activation and apoptosis have been identified as key phenomena of
the immune system destruction.
This book assembles the most recent advances on basic and clinical aspects ofT-cell
activationiapoptosis in HIV infection and their implications for immunotherapy. These data
were presented at an international symposium held on July 11-12, 1994, in Paris. The book
is partitioned into 21 chapters covering four comprehensive fields: 1) T-celllmacrophage
activation and HIV infection; 2) Apoptosis and viropathogenesis of HI V disease; 3) Apop
tosis and immunopathogenesis ofHIV disease; 4) Mediators ofT-cell activationiapoptosis
and therapeutic applications.
We hope that this book will assist the readers in understanding recent advances in
the viro-immunopathogenesis of HI V disease as well as the rationales for potential immune
cell-targeted therapeutic interventions.
Jean-Marie Andrieu
WeiLu
v
ACKNOWLEDGMENTS
We graciously thank Philippe Even, dean of the Faculty of Medicine Necker, Rene
Descartes University for his continuous encouragement and support; Simon Wain-Hobson
(Paris), Sven Britton (Huddinge), Jacques Corbeil (San Diego), and Jean-Claude Ameisen
(Lille) for chairing the different sessions of the symposium. The symposium was supported
by Agence N ationale de Recherches sur Ie SIDA (ARNS) and Association de Recherche pour
Ie Traitement des Seropositifs (ARTS).
vii
CONTENTS
T-CELLIMACROPHAGE ACTIVATION AND HIV INFECTION
1. CD4+ and CD8+ T Lymphocyte Activation in HIV Infection: Implications for
Immune Pathogenesis and Therapy ................................ .
Jeffrey Laurence
2. Markers ofImmune Cell Activation and Disease Progression: Cell Activation in
HIV Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 17
M. Peakman, M. Mahalingam, A. Pozniak, T. 1. McManus, A. N. Phillips,
and D. Vergani
3. The Role of the Cell Cycle in HIV-1 Infection. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 27
Jerome A. Zack
4. Molecular Basis of Cell Cycle Dependent HIV-1 Replication: Implications for
Control of Virus Burden .......................................... 33
M. Stevenson, B. Brichacek, N. Heinzinger, S. Swindells, S. Pirruccello,
E. Janoff, and M. Emerman
5. Regulation of Macrophage Activation and HIV Replication .................. 47
Luis J. Montaner, Georges Herbein, and Siamon Gordon
6. Investigations on Autologous T-Cells for Adoptive Immunotherapy of AIDS .... 57
Jan van Lunzen, Jom Schmitz, Kathrin Dengler, Claudia Kuhlmann,
Herbert Schmitz, and Manfred Dietrich
7. Rational Problems Associated with the Development of Cellular Approaches in
Controlling HIV Spread .......................................... 71
Aldar S. Bourinbaiar and Sylvia Lee-Huang
APOPTOSIS AND VIROPATHOGENESIS OF HIV DISEASE
8. The Role of Surface CD4 in HIV-Induced Apoptosis ........................ 91
Jacques Corbeil and Douglas D. Richman
ix
x Contents
9. Mechanism of Apoptosis in Peripheral Blood Mononuclear Cells ofHIV-Infected
Patients ........................................................ 101
Naoki Oyaizu, Thomas W. Mc Closkey, Soe Than, Rong Hu, and
Savita Pahwa
10. Programmed Death of T Cells in the Course of HIV Infection ................ 115
Linde Meyaard and Frank Miedema
11. T Cell Apoptosis as a Consequence of Chronic Activation of the Immune System
in HIV Infection ................................................ 121
Marie-Lise Gougeon
12. Apoptosis during HIV Infection: A Cytopathic Effect of HIV or an Important
Host-Defense Mechanism against Viruses in General? .................. 129
Seamus J. Martin and Douglas R. Green
APOPTOSIS AND IMMUNOPATHOGENESIS OF HIV DISEASE
13. From Cell Activation to Cell Depletion: The Programmed Cell Death Hypothesis
of AIDS Pathogenesis ............................................ 139
Jean Claude Ameisen
14. Immunosuppression by a Noncytolytic Virus Via T Cell Mediated
Immunopathology: Implication for AIDS ............................ 165
Rolf M. Zinkernagel
15. Clonal Expansion ofT Cells and HIV Genotypes in Microdissected Splenic
White Pulps Indicates Viral Replication in Situ and Infiltration of
HIV-Specific Cytotoxic T Lymphocytes .............................. 173
Remi Cheynier, Sven Henrichwark, Fabienne Hadida, Eric Pelletier,
Eric Oksenhendler, Brigitte Autran, and Simon Wain-Hobson
16. Autoimmunity, Apoptosis Defects, and Retroviruses ........................ 183
1. D. Mountz, 1. Cheng, X. Su, 1. Wu, and T. Zhou
17. AIDS as Immune System Activation: Key Questions that Remain ............. 203
Michael S. Ascher, Haynes W. Sheppard, John F. Krowka and
Hans J. Bremermann
MEDIATORS OF T-CELL ACTIVATION/APOPTOSIS AND
THERAPEUTIC APPLICATIONS
18. Inhibition ofT Lymphocyte Activation and Apoptotic Cell Death by Cyclosporin
A and Tacrolimus (FK506): Its Relevance to Therapy of HIV Infection .... 211
Angus W. Thomson and C. Andrew Bonham
19. Cyclophilin and Gag in HIV-l Replication and Pathogenesis ................. 217
Ettaly Kara Franke and Jeremy Luban
Contents xi
20. Long-Term Follow-up of HI V Positive Asymptomatic Patients Having Received
Cyclosporin A .................................................. 229
Rafael Levy, Jean-Philippe Jais, Jean-Marc Tourani, Philippe Even, and
Jean-Marie Andrieu
21. Prospective Views ofHIV Pathology: Clues for Therapeutic Strategies ......... 235
Wei Lu and Jean-Marie Andrieu
Index ................................................................. 243
1
CD4+ AND CD8+ T LYMPHOCYTE
ACTIVATION IN HIV INFECTION
Implications for Immune Pathogenesis and Therapy
Jeffrey Laurence'
Laboratory for AIDS Virus Research
Cornell University Medical College
New York, New York
INTRODUCTION
Studies initiated some 30 years ago by Dr. Howard Temin demonstrated that the state
of host cell activation at the time ofretroviral infection influences greatly reverse transcrip
tion and viral expression (1). Similarly, helper/inducer (CD4+) and cytolytic (CD4+ and
CD8+) T lymphocyte activation plays a crucial role in the life-cycle of HIY. Indeed, HIV
has adopted a transcriptional strategy resembling that used by certain cellular genes that
regulate T cell signalling and growth (2), as modulated by viral cis and trans-acting elements.
This enables HIV to establish a persistent infection in T cells from which replication
competent virus may be induced through a variety of pathways. Similarly, macrophage
tropic virus, thought responsible for initial infections in humans, establishes a reservoir in
monocytes which is susceptible to differentiation and activation signals (3). Such chronicity
in either cell lineage may not represent true molecular latency, with absent expression of
viral transcripts and protein. Yet latency and viral persistence both involve two essential
elements: initial restriction at the level of proviral transcription or initiation, regulated at
HIV's long terminal repeat (LTR) and, perhaps, through intragenic enhancers (4); and a
second level of control, with the fate of initiated transcripts dependent upon the viral
regulatory elements tat and rev (5). It is also significant that viral replication can be
dissociated from cellular growth, with both proliferative and non-mitogenic T cell activation
signals sufficient to induce HIV transcription (6). The extraordinarily high turnover of HIV
viruses (109/day) and rapid death of productively HIV-infected (tl/2 = 2-15 days) in the
periphery vs. lymph node also attests to the complex regulatory control of HIV replication
(7).
Aberrant T cell activation is another factor in the pathophysiology of HIV disease.
It can be mediated by HIV infection or indirectly, via: incomplete cross-linking or down-
• Requests for reprints to: Jeffrey Laurence, M.D. Cornell University Medical College, 411 E. 69th Street,
Room KB-122, New York, NY 10021, USA.
Cell Activation and Apoptosis in HIV Infection
Edited by Jean-Marie Andrieu and Wei Lu, Plenum Press, New York, 1995 1