Memory T Cells (eBook)

Maurizio Zanetti, Stephen P. Schoenberger (Herausgeber)

eBook Download: PDF

2011 | 2010
XXIII, 203 Seiten
Springer New York (Verlag)
978-1-4419-6451-9 (ISBN)

Infos

Immunological memory has fascinated microbiologists and immunologists for decades as one of the new frontiers to conquer to better understand the response to pathogens, cancer and vaccination. Over the past decade, attention has turned to the intrinsic properties of the memory T cells themselves, as it has become clear that the eradication of both infected cells and tumors requires T cells. This book is an attempt to capture the wave of discoveries associated with these recent studies. Its chapters represent a wide collection of topics related to memory T cells by laboratories that have invested their skills and knowledge to understand the biology and the principles upon which memory T cells are generated, maintained and expanded upon re-encounter with antigen. Ultimately, these studies are all aimed at a better understanding of the function of memory T cells in protection against disease.

Maurizio Zanetti, MD, is a Professor of Medicine at the University of California, San Diego (UCSD), and member of the Moores UCSD Cancer Center. He is the Director of the Immunology laboratory at the Moores UCSD Cancer Center as well as of the Graduate Course in Immunology at UCSD. Main interests include the generation and maintenance of memory T cells with protective value against disease. These responses are studied with respect to cancer and influenza virus infection. His work in humans is devoted to to the immunology of telomerase reverse transcriptase, a prototype universal cancer antigen. He served in the program Committee of the American Society of Immunology, and as Associate Editor for the Journal of Immunology and Cellular Immunology. He is a member of the American Association of Immunologists and American Society for Clinical Investigation. He received his MD from the University of Padova, Italy. Stephen P. Schoenberger, PhD, is a member in the Laboratory of Cellular Immunology at the La Jolla Institute for Allergy and Immunology and adjunct faculty in the division of Hematology and Oncology at the University of California at San Diego School of Medicine. His main research interests include CD8+ T-cell immune memory and antigen presentation cell function. He is a member of the editorial advisory board of Journal of Experimental Medicine, and Associate Editor at the Journal of Immunology, and is a member of numerous national and international scientific organizations including the Dutch Immunology Society, The American Association of Immunologists. He received his PhD from the University of California in Los Angeles, USA.

Inhalt

Title page 3
Copyright page 4
DEDICATION 5
PREFACE 6
ABOUT THE EDITORS 9
PARTICIPANTS 11
Table of Contents 15
ACKNOWLEDGEMENTS 20
Chapter 1 MEMORY TH1/TH2 CELLGENERATION CONTROLLED BY SCHNURRI-2 21
Introduction 21
Schnurri Family Genes 22
Shn-3 23
Shn-2 23
Role of Shn-2 in Naïve CD4 T and Effector Th2 Cells 24
Role of Shn-2 in The Generation of Memory Th1/Th2 Cells 26
NF-kB Overexpression in Effector Th Cells Results in the Decreased Generation of Memory Th Cells 28
Interesting Q uestions Raised by the Study on Shn-2 28
Conclusion 28
Acknowledgements 29
References 29
Chapter 2 TRANSCRIPTIONAL REGULATION DURING CD8 T-CELL IMMUNE RESPONSES 31
The Regulation of Gene Expression: General Rules 31
TF Composition 31
Transcription Requires Multiple TF Binding 31
Mode of Action of DNA Sequence Specific TF 32
The Transcription Apparatus 32
Gene Expression Is Dependent of Complex Regulatory Events 32
The Gene Expression’ Stochastic Component 32
Gene Expression Is Not an “All or Nothing Event” 33
The Gene Regulatory Elements Involved in CD8 Responses 33
Major Regulators of CD8 Function 33
NFAT 33
Other TF Reported to Play a Role in CD8 Responses 34
Transcriptional Repressors (TR) 34
Regulation of Individual Effector Genes 35
Modifications of Gene Expression in CD8 Responses 36
Methodologies to Evaluate Gene Expression by CD8 T cells 36
Population Studies 36
The Importance of Frequency Estimates 37
Predicting Functional Behavior 37
Screening for New Subpopulations 38
Differential Gene Expression during CD8 Responses 39
The Expression of Individual Effector Genes Throughout the Immune Response 39
Different Infections May Induce Different Gene Expression Patterns 42
The Identification of CD8 Subpopulations: Man and Mouse Differ 43
Conclusion 44
References 44
Chapter 3 THE ROLE OF INTERLEUKIN-2 IN MEMORY CD8 CELL DIFFERENTIATION 48
Introduction 48
IL-2 Signals during Priming Lead to Q ualitative and Q uantitative Differences in CD8 T-Cell Responses 50
Memory Cell Generation and Recall Responses 57
Memory Maintenance and Homeostasis 57
Indirect Roles of IL-2 in the Generation of Memory CD8 T Cells 58
Conclusion 58
References 58
Chapter 4 THE ROLE OF INFLAMMATION IN THE GENERATION AND MAINTENANCE OF MEMORY T CELLS 62
Introduction 62
The Role of Inflammation during T-Cell Priming and Expansion 64
Inflammation and T-Cell Contraction 66
Inflammation Regulates the Rate of Memory T-Cell Generation 68
Memory T-Cell Maintenance 71
Conclusion 72
Acknowledgements 72
References 72
Chater 5 THE ROLE OF OX40 (CD134) IN T-CELL MEMORY GENERATION 77
Introduction 77
Background 78
Role of OX40/OX40L Interaction in Memory T-Cell Generation and Function 79
Providing an Exogenous OX40 Signal (OX40 Agonists) to Enhance Memory T-Cell Generation 80
Altering Memory T-Cell Generation/Function through the OX40Axis for Therapeutic Benefit in Autoimmunity, Cancer and HostsHarboring Chronic Pathogens 83
Conclusion 85
References 86
Chapter 6 THE ROLE OF PRECURSOR FREQUENCY IN THE DIFFERENTIATION OF MEMORY T CELLS: MEMORY BY NUMBERS 89
History of Immunological Memory 89
Inroads into Understanding T Memory Development 90
Use of TCR Transgenics to Elucidate T-Cell Biology 92
Precursor Frequency Affects Memory T-Cell Development 92
One Cell, Many Fates 95
Which Are the Better Protectors? 96
Conclusion 96
Acknowledgements 97
References 97
Chapter 7 CD8 T-CELL MEMORY DIFFERENTIATION DURING ACUTE AND CHRONIC VIRAL INFECTIONS 99
Introduction 99
CD8 T-Cell Responses following Acute Infection 100
Programming during the Expansion Phase 101
Selective Survival of Memory Precursors during the Contraction Phase 103
Memory CD8 T-Cell Differentiation and Heterogeneity 103
Molecular Basis of Optimal Memory Functions 104
Models of Memory CD8 T-Cell Differentiation 105
Mechanisms Regulating Memory CD8 T-Cell Heterogeneity 106
CD8 T-Cell Responses following Persistent Infection 108
Functional Exhaustion of CD8 T Cells during Chronic Infections 109
Altered Memory CD8 T-Cell Homeostasis 109
Mechanisms of CD8 T-Cell Exhaustion 110
Conclusion 111
References 111
Chapter 8 LONGEVITY OF T-CELL MEMORY FOLLOWING ACUTE VIRAL INFECTION 116
Introduction 116
Memory T-Cell Responses following Acute Viral Infection 118
Functional Attributes of Human Memory T Cells 122
Conclusion 124
Acknowledgements 124
References 125
Chapter 9 PRINCIPLES OF MEMORY CD8 T-CELLS GENERATION IN RELATION TO PROTECTIVE IMMUNITY 128
Introduction 128
T-Cell Immunity—From Activation to Imprinting T-Cell Memory 129
Considerations on the Parameters of the Primary ResponseThat Influence the Generation of Memory T Cells 131
Memory CD8 T-Cell Subpopulations, Lineage Commitment and Protective Responses 132
Memory CD8 T Cells Induced by Low Antigen Dose VaccinationProtect Mice from Influenza a Virus Infection—The Role of CD62hiMemory CD8 T (TCM) Cells 133
Central Memory CD8 T Cells Correlate with Protection against SIV in Rhesus Macaques 135
Principles for Programming Protective T-Cell Responses by Vaccination in the Immunologically Inexperienced Individual 135
Principles for Reprogramming Protective T-Cell Responses by Vaccination in the Immunologically Experienced Individual 138
The Role of Local Immunity in Protection by Memory CD8 T Cells 138
Conclusion 141
Acknowledgements 142
References 142
Chapter 10 Contents 10. MEMORY T CELLS IN RHESUS MACAQUES 146
Introduction 146
Memory T Cells in Rhesus Macaques 147
Phenotypic Characterization of T-Cell Memory Subsets 147
Central and Effector Memory T Cells 148
T Regulatory Cells and Th17 148
Tissue Distribution of T-Cell Memory Subsets in Rhesus Macaques 150
Peripheral Blood and Lymph Nodes 151
The Gastrointestinal Tract 151
The Lung 152
The Vaginal Mucosa 152
In Vivo Manipulation of Memory T Cells in Non-Human Primates 152
Autologous Transfer 152
In Vivo Studies of T-Cell Turnover 153
Thymectomy 153
In Vivo Depletion of T-Cells Subsets 153
Blocking Antibodies In Vivo 155
Differentiation of Memory T-Cells Subsets: Lesson from In Vivo Studies in Non-Human Primates 156
Aging of T Memory Cells 157
Conclusion 158
Acknowledgements 158
References 159
Chapter 11 MEMORY T-CELL SUBSETS IN PARASITIC INFECTIONS 165
Introduction 165
What Are the Challenges for the Development of Parasite Vaccines? 167
Th1 Immunity: Balancing Resistance and Persistence in Parasitic Infections 168
Th2 Immunity: Longer Lasting Than Th1 Memory? 170
Memory T Cells in Malaria 171
Conclusion 172
Acknowledgements 172
References 172
Chapter 12 ANTIGEN SPECIFIC MEMORY T CELLS AND THEIR PUTATIVE NEED FOR THE GENERATION OF SUSTAINED ANTI-TUMOR RESPONSES 175
Introduction 175
The Difficulties Facing Potent and Sustained Immune Responsesto Cancer 176
Evidence for Immune Responses to Cancer in Man 177
Immune Responses to Tumors in Mouse Models 177
Is Immunological Memory Important for Tumor Regression or Tumor Equilibrium? 179
Lacking T-Cell Memory after Strong Immune Stimulation 180
Conclusion 182
References 183
Chapter 13 MEMORY T-CELL RESPONSES AND SURVIVAL IN HUMAN CANCER: REMEMBER TO STAY ALIVE 186
Introduction 186
Characteristics of Tumor Antigen-Specific T Cells 187
Global Analysis of the Immune Reaction in Colorectal Cancer:A Breakthrough for Patient Prognosis 188
Th1 Adaptive Immune Responses and Patient Survival 188
Effector-Memory T Cells and Early Metastatic Invasion 189
In Situ Coordination of Immune Reaction and Improved Prognostic Evaluation 190
A Long-Term Memory against Cancer? 191
Perspectives for Cancer Research and Treatment Strategies 192
Conclusion 193
References 194
Chapter 14 ANALYSIS OF VACCINE-INDUCED T CELLS IN HUMANS WITH CANCER 198
Methods for Immune Monitoring following Active-Specific Immunization 200
Systemic Response 200
Limiting Dilution Assays (LDA) 200
Enzyme-Linked Immunospot Assays (ELISPOT) 201
Cytokine Flow Cytometry (CFC) 201
Tetramer Analysis with Soluble Major Histocompatibility Complex (MHC)/Peptide Complexes 202
Quantitative Reverse Transcription-Polymerase Chain Reaction 202
Transcriptional Analysis of Circulating T Cells Following Active-Specific Immunization 203
Tumor-Site Response, Tumor Microenvironment 203
The Immune Surveillance Hypothesis 203
Transcriptional Profiling Immune Responses against Tumors 203
Conclusion 205
References 206
Chapter 15 MEMORY T-CELL HOMEOSTASIS AND SENESCENCE DURING AGING 209
Introduction 209
Phenotypic and Functional Differentiation of T Cells during Aging 209
Telomere Erosion and T-Cell Memory 211
Telomerase Regulation in Differentiated T Cells 212
Loss of T-Cell Memory during Aging 212
Conclusion 214
References 214
INDEX 218

Produkt-Details

• Erscheint lt. Verlag: 11.1.2011
• Reihe/Serie: Advances in Experimental Medicine and Biology
• Reihe/Serie: Advances in Experimental Medicine and Biology
• Zusatzinfo: XXIII, 203 p.
• Verlagsort: New York
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Neurologie
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Physiologie
• Themenwelt: Naturwissenschaften ► Biologie
• Themenwelt: Technik
• Schlagworte: Antigen • Cell • Cells • Infections • Memory • Regulation • Schoenberger • Zanetti
• ISBN-10: 1-4419-6451-7 / 1441964517
• ISBN-13: 978-1-4419-6451-9 / 9781441964519