Dendritic Cells in Clinics

199 Pages·2008·1.16 MB·English

by  Morikazu Onji M.D. PH.D.

M. Onji, S.M.F. Akbar
Dendritic Cells in Clinics
2nd Edition
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M. Onji, S.M.F. Akbar
Dendritic Cells
in Clinics
2
nd Edition
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Morikazu Onji, M.D. PH.D.
Professor, Department of Gastroenterology and Metabology, Ehime University Graduate
School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan
Sk. Md. Fazle Akbar, MBBS, PH.D.
Department of Gastroenterology and Metabology, Ehime University Graduate School of
Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan
ISBN 978-4-431-79465-3 Springer Tokyo Berlin Heidelberg New York
Library of Congress Control Number: 2008928563
© Morikazu Onji and Sk. Md. Fazle Akbar 2008
This work is subject to copyright. All rights are reserved, whether the whole or part of the material
is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broad-
casting, reproduction on microfi lms or in other ways, and storage in data banks.
The use of registered names, trademarks, etc. in this publication does not imply, even in the absence
of a specifi c statement, that such names are exempt from the relevant protective laws and regulations
and therefore free for general use.
Product liability: The publisher can give no guarantee for information about drug dosage and appli-
cation thereof contained in this book. In every individual case the respective user must check its
accuracy by consulting other pharmaceutical literature.
Springer is a part of Springer Science+Business Media
springer.com
Printed in Japan
Typesetting: SNP Best-set Typesetter Ltd., Hong Kong
Printing and binding: Kato Bunmeisha, Japan
Printed on acid-free paper
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In Commemoration of
The 44th Annual Meeting of the Japan Society of Hepatology 2008
Matsuyama, Japan
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Foreword
It now has been clearly recognized that dendritic cells play a crucial role in the initia-
tion and modulation of immune responses against infectious diseases and cancers;
they are involved in both innate and acquired immunity. Since the identifi cation of
myeloid dendritic cells by Steinman and Cohn in 1973, a huge volume of fi ndings on
dendritic cells has been obtained. It is known that there are subsets of dendritic cells
with different phenotypes and functions, and the phenotypes and functions of indi-
vidual dendritic cells have been studied extensively and been clarifi ed. On the basis
of this cumulative research, dendritic cells are thought to be a possible potent adju-
vant for both prophylactic and therapeutic vaccine against infectious diseases and
cancers.
Five years ago, Professor Onji and his colleagues, Drs. Akbar and Horiike, pub-
lished the fi rst edition of Dendritic Cells in Clinics. The book was astonishing to me
as the authors beautifully summarized a huge amount of information on dendritic
cells and immunology for any reader to understand. Five years have passed since the
publication of the fi rst edition, and during that time the advances in the fi eld have
been tremendous. I know quite well that Professor Onji and Dr. Akbar, both talented
physician–scientists, have worked very hard in this fi eld and have sought to apply an
understanding of dendritic cells to the prevention and treatment of liver diseases.
Thus it is timely for them to publish the second edition of the book at this moment.
Thanks to Professor Onji and Dr. Akbar, we now have available in this book the
latest knowledge on dendritic cells and its possible application in clinics. As Professor
Onji’s colleague in the study of liver immunology and as a longstanding friend, it is
my great honor to write this foreword.
Michio Imawari, M.D.
Professor and Chairman
Department of Medicine
Chief, Division of Gastroenterology
Showa University School of Medicine
Tokyo
VII
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Preface
Dramatic changes have taken place in politics and economics in Japan during the last
5 years, and comparable changes have occurred in medical service delivery systems
and education. New clinical training curricula following graduation from medical
schools have brought revolutionary changes in medical education and the clinical
research system. Although there has been some stagnancy in the nature of ongoing
medical research in Japan, I believe that opportunities for great future developments
are being provided. Recent successes in the development of stem cells and their pos-
sible applications in clinics inspire researchers in all fi elds.
The fi rst edition of this book was published in 2004, when many clinicians had
begun showing an interest in dendritic cells. It was one of the fi rst books about den-
dritic cells that described their relevance in clinical medicine. After its publication,
we received many enthusiastic responses and also many criticisms. During the past
5 years, great advances have taken place in basic research and the clinical usefulness
of dendritic cells. When the fi rst edition was published, the plasmacytoid dendritic
cell was an important topic in the clinical fi eld, and the role of dendritic cells beyond
that of T cell priming began to unfold. During the last few years, type-1 interferon-
producing dendritic cells have provided more support to the idea that dendritic cells
are essential to innate immunity. Discovery of different pattern receptors, including
Toll-like receptors on dendritic cells, has fi rmly established the position of these cells
in regulating innate immunity. Concurrently, it has been revealed that immune toler-
ance plays a critical role in controlling the immune system in living organisms and
that critical events in this cascade are controlled by dendritic cells. Researchers have
shown that regulatory dendritic cells prepared in vitro induce antigen-specifi c
immune tolerance. Knowledge of regulatory dendritic cells defi nitely contributes to
an understanding of pathogenesis and of the development of new therapy against
immune-associated diseases. Thus, dendritic cells, the mighty immunocytes, induce
both innate and adaptive immunity as well as regulating immune responses and
immune tolerance.
These advances in dendritic cell biology led to the revision of the fi rst edition of
Dendritic Cells in Clinics, with an eye toward clarifying the implications of dendritic
cells in the pathogenesis and treatment of human diseases. We have been working
with dendritic cells for more than two decades, but our major focus is on liver immu-
nology. We therefore feel a natural responsibility to respond to queries about den-
dritic cells in clinics during the 44th Annual Meeting of the Japan Society of Hepatology
in June of 2008, to be organized by me and other members of our department at
IX
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X Preface
Matsuyama, Japan. In this context, I hope that the newly published 2nd edition of
Dendritic Cells in Clinics will provide some answers to questions about dendritic cells
for use in humans.
We would like to express my gratitude to my colleagues in our department and to
the members of our Yellow Orchard Club.
Morikazu Onji
Sk. Md. Fazle Akbar
January 2008
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Contents
Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . VII
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . IX
1. History of Dendritic Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
From Discovery to Clinical Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
2. General Features of Dendritic Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Dendritic Cells in Clinical Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Outline of DCs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Defi nition of DCs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
Origin and Development of DCs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Detection of DC-Like Cells in the Intrauterine Life of
Mouse and Man . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Origin of DCs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Regulation of DC Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Dendritic Cells in Different Organs and Tissues . . . . . . . . . . . . . . . . . . . . . . . 24
DCs in Lymphoid Organs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
DC in the Nonlymphoid Tissues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Clinical Implications of Phenotypes and Subsets of DCs . . . . . . . . . . . . . . . 31
Function of Dendritic Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
DCs in Innate Immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
DC in Adaptive Immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
Antigen Presentation and T-Cell Activation . . . . . . . . . . . . . . . . . . . . . . . . . . 36
Clinical Implications of DC Functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
Concluding Remarks: Implications of This Chapter in the Clinic . . . . . . . 37
Recommended Readings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
3. Interactions Between Dendritic Cells and Infectious Agents . . . . . . . . . . . . 41
Outline of Dendritic Cell in Microbial Infection . . . . . . . . . . . . . . . . . . . . . . 41
Consequences of Interactions Between DC and Virus . . . . . . . . . . . . . . . . . 49
Interactions Between Dendritic Cells and Bacteria . . . . . . . . . . . . . . . . . . . . 67
Recommended Readings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
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XII Contents
4. Dendritic Cells and Allergy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
Nature of Immune Responses and Allergic Diseases . . . . . . . . . . . . . . . . . . . 73
Pathogenesis of Allergic Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
Dendritic Cells in Allergy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
Allergen-Specifi c Immune Responses and Memory Lymphocyte
Formation by DCs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76
Th2 Polarization Capacities of Both Myeloid and Plasmacytoid DCs . . . . 78
Dendritic Cells and Drug Allergy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
Dendritic Cells in Animal Models of Allergy . . . . . . . . . . . . . . . . . . . . . . . . . 80
Removal of Airway DCs from Sensitized Mice Eliminates
Asthmatic Features Induced by Antigen Aerosol . . . . . . . . . . . . . . . . . . . 80
Dendritic Cells in Human Allergy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Allergic Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
Atopic Dermatitis (AD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
Allergic Rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
Treatment of Allergic Conditions by DCs . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
Recommended Readings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
5. Dendritic Cells and Autoimmunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
General Consideration of Autoimmunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
Dendritic Cells in Autoimmunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
Goal of DC Research in Autoimmune Diseases . . . . . . . . . . . . . . . . . . . . . . . 91
DCs in the Pathogenesis of Autoimmune Diseases . . . . . . . . . . . . . . . . . . . . 92
Putative Role of DCs in Induction of Autoimmunity . . . . . . . . . . . . . . . . . . 95
DCs at the Tissues in Autoimmune Conditions . . . . . . . . . . . . . . . . . . . . . . . 95
Peripheral Blood DCs in Autoimmune Diseases . . . . . . . . . . . . . . . . . . . . . . 97
IFN-α and Plasmacytoid DCs in Autoimmune Diseases . . . . . . . . . . . . . . . . 98
DC-Based Therapy for Autoimmunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
DC-Based Therapy in Animal Models of Human
Autoimmune Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Possible Use of DCs for Treatment of Human Autoimmune Diseases . . . 101
Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
Recommended Readings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
6. Dendritic Cells in Tumor Immunology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Basic Principles of Tumor Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Dendritic Cells and Tumor Immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107
Localization and Characterization of DCs in Tumors . . . . . . . . . . . . . . . . . . 121
Immune Therapy of Tumors Using Dendritic Cells . . . . . . . . . . . . . . . . . . . 126
DC-Based Therapy for Human Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128
Recommended Readings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
7. Dendritic Cells in Transplantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
Present Status of Organ Transplantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
Acute and Chronic Rejection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
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