Zanetti / Schoenberger Memory T Cells

1. Auflage 2011
ISBN: 978-1-4419-6451-9
Verlag: Springer US
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band 684, 198 Seiten

Reihe: Advances in Experimental Medicine and Biology

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.

Autoren/Hrsg.

Zanetti, Maurizio

Schoenberger, Stephen P.

Inhaltsverzeichnis

1;Title page ;3
2;Copyright page ;4
3;DEDICATION;5
4;PREFACE;6
5;ABOUT THE EDITORS;9
6;PARTICIPANTS;11
7;Table of Contents;15
8;ACKNOWLEDGEMENTS;20
9;Chapter 1 MEMORY TH1/TH2 CELLGENERATION CONTROLLED BY SCHNURRI-2;21
9.1;Introduction;21
9.2;Schnurri Family Genes;22
9.3;Shn-3;23
9.4;Shn-2;23
9.5;Role of Shn-2 in Naïve CD4 T and Effector Th2 Cells;24
9.6;Role of Shn-2 in The Generation of Memory Th1/Th2 Cells;26
9.7;NF-kB Overexpression in Effector Th Cells Results in the Decreased Generation of Memory Th Cells;28
9.8;Interesting Q uestions Raised by the Study on Shn-2;28
9.9;Conclusion;28
9.10;Acknowledgements;29
9.11;References;29
10;Chapter 2 TRANSCRIPTIONAL REGULATION DURING CD8 T-CELL IMMUNE RESPONSES;31
10.1;The Regulation of Gene Expression: General Rules;31
10.1.1;TF Composition;31
10.1.2;Transcription Requires Multiple TF Binding;31
10.1.3;Mode of Action of DNA Sequence Specific TF;32
10.1.4;The Transcription Apparatus;32
10.1.5;Gene Expression Is Dependent of Complex Regulatory Events;32
10.1.6;The Gene Expression’ Stochastic Component;32
10.1.7;Gene Expression Is Not an “All or Nothing Event”;33
10.2;The Gene Regulatory Elements Involved in CD8 Responses;33
10.2.1;Major Regulators of CD8 Function;33
10.3;NFAT;33
10.3.1;Other TF Reported to Play a Role in CD8 Responses;34
10.3.2;Transcriptional Repressors (TR);34
10.3.3;Regulation of Individual Effector Genes;35
10.4;Modifications of Gene Expression in CD8 Responses;36
10.4.1;Methodologies to Evaluate Gene Expression by CD8 T cells;36
10.5;Population Studies;36
10.6;The Importance of Frequency Estimates;37
10.7;Predicting Functional Behavior;37
10.8;Screening for New Subpopulations;38
10.8.1;Differential Gene Expression during CD8 Responses;39
10.8.2;The Expression of Individual Effector Genes Throughout the Immune Response;39
10.9;Different Infections May Induce Different Gene Expression Patterns;42
10.10;The Identification of CD8 Subpopulations: Man and Mouse Differ;43
10.11;Conclusion;44
10.12;References;44
11;Chapter 3 THE ROLE OF INTERLEUKIN-2 IN MEMORY CD8 CELL DIFFERENTIATION;48
11.1;Introduction;48
11.1.1;IL-2 Signals during Priming Lead to Q ualitative and Q uantitative Differences in CD8 T-Cell Responses;50
11.1.2;Memory Cell Generation and Recall Responses;57
11.1.3;Memory Maintenance and Homeostasis;57
11.1.4;Indirect Roles of IL-2 in the Generation of Memory CD8 T Cells;58
11.2;Conclusion;58
11.3;References;58
12;Chapter 4 THE ROLE OF INFLAMMATION IN THE GENERATION AND MAINTENANCE OF MEMORY T CELLS;62
12.1;Introduction;62
12.2;The Role of Inflammation during T-Cell Priming and Expansion;64
12.3;Inflammation and T-Cell Contraction;66
12.4;Inflammation Regulates the Rate of Memory T-Cell Generation;68
12.5;Memory T-Cell Maintenance;71
12.6;Conclusion;72
12.6.1;Acknowledgements;72
12.7;References;72
13;Chater 5 THE ROLE OF OX40 (CD134) IN T-CELL MEMORY GENERATION;77
13.1;Introduction;77
13.2;Background;78
13.3;Role of OX40/OX40L Interaction in Memory T-Cell Generation and Function;79
13.4;Providing an Exogenous OX40 Signal (OX40 Agonists) to Enhance Memory T-Cell Generation;80
13.5;Altering Memory T-Cell Generation/Function through the OX40Axis for Therapeutic Benefit in Autoimmunity, Cancer and HostsHarboring Chronic Pathogens;83
13.6;Conclusion;85
13.7;References;86
14;Chapter 6 THE ROLE OF PRECURSOR FREQUENCY IN THE DIFFERENTIATION OF MEMORY T CELLS: MEMORY BY NUMBERS;89
14.1;History of Immunological Memory;89
14.2;Inroads into Understanding T Memory Development;90
14.3;Use of TCR Transgenics to Elucidate T-Cell Biology;92
14.4;Precursor Frequency Affects Memory T-Cell Development;92
14.5;One Cell, Many Fates;95
14.6;Which Are the Better Protectors?;96
14.7;Conclusion ;96
14.7.1;Acknowledgements;97
14.8;References;97
15;Chapter 7 CD8 T-CELL MEMORY DIFFERENTIATION DURING ACUTE AND CHRONIC VIRAL INFECTIONS;99
15.1;Introduction;99
15.2;CD8 T-Cell Responses following Acute Infection;100
15.2.1;Programming during the Expansion Phase;101
15.2.2;Selective Survival of Memory Precursors during the Contraction Phase;103
15.2.3;Memory CD8 T-Cell Differentiation and Heterogeneity;103
15.2.4;Molecular Basis of Optimal Memory Functions;104
15.2.5;Models of Memory CD8 T-Cell Differentiation;105
15.2.6;Mechanisms Regulating Memory CD8 T-Cell Heterogeneity;106
15.3;CD8 T-Cell Responses following Persistent Infection;108
15.3.1;Functional Exhaustion of CD8 T Cells during Chronic Infections;109
15.3.2;Altered Memory CD8 T-Cell Homeostasis;109
15.3.3;Mechanisms of CD8 T-Cell Exhaustion;110
15.4;Conclusion;111
15.5;References;111
16;Chapter 8 LONGEVITY OF T-CELL MEMORY FOLLOWING ACUTE VIRAL INFECTION;116
16.1;Introduction;116
16.2;Memory T-Cell Responses following Acute Viral Infection;118
16.3;Functional Attributes of Human Memory T Cells;122
16.4;Conclusion;124
16.4.1;Acknowledgements;124
16.5;References;125
17;Chapter 9 PRINCIPLES OF MEMORY CD8 T-CELLS GENERATION IN RELATION TO PROTECTIVE IMMUNITY;128
17.1;Introduction;128
17.2;T-Cell Immunity—From Activation to Imprinting T-Cell Memory;129
17.3;Considerations on the Parameters of the Primary ResponseThat Influence the Generation of Memory T Cells;131
17.4;Memory CD8 T-Cell Subpopulations, Lineage Commitment and Protective Responses;132
17.5;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
17.6;Central Memory CD8 T Cells Correlate with Protection against SIV in Rhesus Macaques;135
17.7;Principles for Programming Protective T-Cell Responses by Vaccination in the Immunologically Inexperienced Individual;135
17.8;Principles for Reprogramming Protective T-Cell Responses by Vaccination in the Immunologically Experienced Individual;138
17.9;The Role of Local Immunity in Protection by Memory CD8 T Cells;138
17.10;Conclusion ;141
17.10.1;Acknowledgements;142
17.11;References;142
18;Chapter 10 Contents 10. MEMORY T CELLS IN RHESUS MACAQUES;146
18.1;Introduction;146
18.2;Memory T Cells in Rhesus Macaques;147
18.2.1;Phenotypic Characterization of T-Cell Memory Subsets;147
18.2.1.1;Central and Effector Memory T Cells;148
18.2.1.2;T Regulatory Cells and Th17;148
18.2.2;Tissue Distribution of T-Cell Memory Subsets in Rhesus Macaques;150
18.2.2.1;Peripheral Blood and Lymph Nodes;151
18.2.2.2;The Gastrointestinal Tract;151
18.2.2.3;The Lung;152
18.2.2.4;The Vaginal Mucosa;152
18.3;In Vivo Manipulation of Memory T Cells in Non-Human Primates;152
18.3.1;Autologous Transfer;152
18.3.2;In Vivo Studies of T-Cell Turnover;153
18.3.3;Thymectomy;153
18.3.4;In Vivo Depletion of T-Cells Subsets;153
18.3.5;Blocking Antibodies In Vivo;155
18.4;Differentiation of Memory T-Cells Subsets: Lesson from In Vivo Studies in Non-Human Primates;156
18.5;Aging of T Memory Cells;157
18.6;Conclusion;158
18.6.1;Acknowledgements;158
18.7;References;159
19;Chapter 11 MEMORY T-CELL SUBSETS IN PARASITIC INFECTIONS;165
19.1;Introduction;165
19.2;What Are the Challenges for the Development of Parasite Vaccines?;167
19.3;Th1 Immunity: Balancing Resistance and Persistence in Parasitic Infections;168
19.4;Th2 Immunity: Longer Lasting Than Th1 Memory?;170
19.5;Memory T Cells in Malaria;171
19.6;Conclusion;172
19.6.1;Acknowledgements;172
19.7;References;172
20;Chapter 12 ANTIGEN SPECIFIC MEMORY T CELLS AND THEIR PUTATIVE NEED FOR THE GENERATION OF SUSTAINED ANTI-TUMOR RESPONSES;175
20.1;Introduction;175
20.2;The Difficulties Facing Potent and Sustained Immune Responsesto Cancer;176
20.3;Evidence for Immune Responses to Cancer in Man;177
20.4;Immune Responses to Tumors in Mouse Models;177
20.5;Is Immunological Memory Important for Tumor Regression or Tumor Equilibrium?;179
20.6;Lacking T-Cell Memory after Strong Immune Stimulation;180
20.7;Conclusion;182
20.8;References;183
21;Chapter 13 MEMORY T-CELL RESPONSES AND SURVIVAL IN HUMAN CANCER: REMEMBER TO STAY ALIVE;186
21.1;Introduction;186
21.2;Characteristics of Tumor Antigen-Specific T Cells;187
21.3;Global Analysis of the Immune Reaction in Colorectal Cancer:A Breakthrough for Patient Prognosis;188
21.3.1;Th1 Adaptive Immune Responses and Patient Survival;188
21.3.2;Effector-Memory T Cells and Early Metastatic Invasion;189
21.3.3;In Situ Coordination of Immune Reaction and Improved Prognostic Evaluation;190
21.3.4;A Long-Term Memory against Cancer?;191
21.4;Perspectives for Cancer Research and Treatment Strategies;192
21.5;Conclusion;193
21.6;References;194
22;Chapter 14 ANALYSIS OF VACCINE-INDUCED T CELLS IN HUMANS WITH CANCER;198
22.1;Methods for Immune Monitoring following Active-Specific Immunization;200
22.1.1;Systemic Response;200
22.1.2;Limiting Dilution Assays (LDA);200
22.1.3;Enzyme-Linked Immunospot Assays (ELISPOT);201
22.1.4;Cytokine Flow Cytometry (CFC);201
22.1.5;Tetramer Analysis with Soluble Major Histocompatibility Complex (MHC)/Peptide Complexes;202
22.1.6;Quantitative Reverse Transcription-Polymerase Chain Reaction;202
22.1.7;Transcriptional Analysis of Circulating T Cells Following Active-Specific Immunization ;203
22.2;Tumor-Site Response, Tumor Microenvironment;203
22.2.1;The Immune Surveillance Hypothesis;203
22.2.2;Transcriptional Profiling Immune Responses against Tumors;203
22.3;Conclusion;205
22.4;References;206
23;Chapter 15 MEMORY T-CELL HOMEOSTASIS AND SENESCENCE DURING AGING;209
23.1;Introduction;209
23.2;Phenotypic and Functional Differentiation of T Cells during Aging;209
23.3;Telomere Erosion and T-Cell Memory;211
23.4;Telomerase Regulation in Differentiated T Cells;212
23.5;Loss of T-Cell Memory during Aging;212
23.6;Conclusion;214
23.7;References;214
24;INDEX ;218