Biology of Dendritic Cells and HIV Infection (eBook)

Preface 6
Acknowledgments 8
Contents 9
Contributors 19
General Aspects of Dendritic Cell Biology, Functions, and Clinical Application 24
Chapter 1 25
Dendritic Cell Biology: Subset Heterogeneity and Functional Plasticity 25
1.1 Introduction 25
1.2 Origin and Development of Human DC Subsets 26
1.3 Anatomic, Phenotypic, and Functional Features of DC Subsets 29
1.4 Innate Functions of DC Subsets 33
1.5 Role of DC Subsets in Adaptive Immunity 40
1.6 DCs and Tolerance 45
1.7 Concluding Remarks 47
References 47
Chapter 2 66
Dendritic Cells and Their Role in Linking Innate and Adaptive Immune Responses 66
2.1 Introduction 66
2.2 DC Origins, Subsets, and Differentiation 67
2.3 Plasticity and Trafficking Pathways 72
2.4 DC–T Cell Interactions 76
2.5 DCs Link Innate and Acquired Immunity 82
2.6 Concluding Remarks 90
References 91
Chapter 3 106
Dendritic Cell and Pathogen Interactions in the Subversion of Protective Immunity 106
3.1 Introduction 106
3.2 Dendritic Cell Biology 107
3.3 Subversion of Dendritic Cell Function by Pathogens 120
3.4 Concluding Remarks 131
References 131
Chapter 4 150
Dendritic Cells as Keepers of Peripheral Tolerance 150
4.1 Introduction 150
4.2 The Concept of “Steady State” versus “ Activated” DC 151
4.3 Factors That Affect Tolerogenic DCs 157
4.4 Molecular Mechanisms Involved in Tolerance Induction 165
4.5 Are There Specialized Subsets of Tolerogenic DCs? 172
4.6 “Designer DC”: Tailored for Tolerance Induction 175
4.7 Concluding Remarks 179
References 180
Chapter 5 192
Adjuvants, Dendritic Cells, and Cytokines: Strategies for Enhancing Vaccine Efficacy 192
5.1 Introduction 192
5.2 Brief Historical Background on Adjuvants 193
5.3 The Need of New Adjuvants for Vaccine Development and Crucial Importance of Adjuvant– Dendritic Cell Interactions for the Polarization of Immune Response 196
5.4 New Classification of Vaccine Adjuvants 200
5.5 Ligands for TLRs and Their Potential Role as Adjuvants 204
5.6 Interaction of Cytokines with DCs: Importance for Vaccine Development 208
5.7 Concluding Remarks 215
References 216
Chapter 6 224
Ex Vivo–Generated Dendritic Cells for Clinical Trials versus In Vivo Targeting to Dendritic Cells: Critical Issues 224
6.1 Introduction 224
6.2 DC Culture, from Bench to Clinical-Grade Product 226
6.3 DC Quality Check 235
6.4 Vaccine Administration 237
6.5 Immunomonitoring 237
6.6 Targeting DCs In Vivo 239
6.7 Concluding Remarks 250
References 250
General Aspects of the Pathogenesis and Immune Response to HIV- 1 Infection 264
Chapter 7 265
Immunopathogenesis of HIV Infection 265
7.1 Introduction 265
7.2 The Life Cycle of HIV-1 in CD4+ T Cells and Mononuclear Phagocytes 266
7.3 CCR5- versus CXCR4-dependent HIV-1 Infections 272
7.4 Intrinsic Resistance to HIV Infection 279
7.5 HIV Cytopathicity 281
7.6 HIV Replication in Lymphoid Organs and Central Nervous System 285
7.7 Host Determinants of HIV Propagation: Cytokines and Chemokines 288
7.8 Concluding Remarks 293
References 294
Chapter 8 316
Innate Cellular Immune Responses in HIV Infection 316
8.1 Characteristics of Innate Immunity 316
8.2 Cells and Soluble Factors Involved in Innate Immunity Against HIV 318
8.3 Plasmacytoid and Myeloid Dendritic Cells and Their Association with HIV Infection 320
8.4 The Role of Noncytotoxic CD8+ T Cells in Anti- HIV Responses 326
8.5 Other Innate Immune Cells 331
8.6 Concluding Remarks 335
References 336
Chapter 9 352
Adaptative Immune Responses in HIV-1 Infection 352
9.1 Introduction to the Characteristics of Specific Immunity 352
9.2 Functional Immune Disregulation in the Different Phases of HIV- 1 Infection 353
9.3 Cellular Immune Response to HIV-1 355
9.4. Humoral Immune Responses in HIV-1 Infection 370
9.5 Immune Responses in HIV-Exposed Seronegative Individuals 376
9.6 Immune Responses in Long-Term Nonprogressors 378
9.7 Concluding Remarks 380
References 381
Dendritic Cells and HIV Interactions and Their Role in Pathogenesis and Immunity 398
Chapter 10 399
Binding and Uptake of HIV by Dendritic Cells and Transfer to T Lymphocytes: Implications for Pathogenesis 399
10.1 Introduction 399
10.2 Transmission of HIV 399
10.3 HIV Infection of Female Genital Tract 400
10.4 The Role of Dendritic Cells in HIV Infection 402
10.5 Transmission of HIV to T Cells by DCs 408
10.6 Models for Examining HIV Infection and Testing of Vaginal Microbicides in the Genital Mucosa 414
10.7 Concluding Remarks 416
References 417
Chapter 11 423
Loss, Infection, and Dysfunction of Dendritic Cells in HIV Infection 423
11.1 Overview 423
11.2 Introduction to Myeloid and Plasmacytoid DCs 424
11.3 Practical Issues in DC Research 429
11.4 Differentiation of Blood Myeloid DCs 430
11.5 DCs and Transmission of HIV 433
11.6 Loss of DCs in HIV Infection 434
11.7 Infection of DCs by HIV 438
11.8 Dysfunction of DCs in HIV Infection 445
11.9 Concluding Remarks 450
References 451
Chapter 12 465
HIV Exploitation of DC Biology to Subvert the Host Immune Response 465
12.1 Introduction 465
12.2 The Host Response to Viral Infection 466
12.3 Virus-induced Phenotypic and Functional Alterations of Human DCs 472
12.4 DCs in HIV Pathogenesis: Protective or Defective? 477
12.5 Concluding Remarks 492
References 492
Chapter 13 503
Cross-Presentation by Dendritic Cells: Role in HIV Immunity and Pathogenesis 503
13.1 Introduction 503
13.2 Antigen Presentation Pathways 503
13.3 Direct Presentation of HIV from Infected DCs 507
13.4 Cross-Presentation of HIV 508
13.5 Comparison of Cross-Presentation from Live or from Dead Cells 514
13.6 Role of Cross-Presentation from Infected Cells in HIV Immunity and Pathogenesis 517
13.7 Concluding Remarks 519
References 520
Chapter 14 533
Immunotherapy of HIV Infection: Dendritic Cells as Targets and Tools 533
14.1 Introduction 533
14.2 The Rationale for Combining HAART with Immunotherapy in the Treatment of HIV- 1 Infection 534
14.3 Overview of the Clinical Trials of Immunotherapy for the Treatment of HIV- 1 Infection 537
14.4 The Dendritic Cell as Target for the Development of HIV- 1 Vaccines 542
14.5 Dendritic Cells as Tools for the Development of Therapeutic Vaccines Against HIV 544
14.6 Concluding Remarks 551
References 552
Index 559