Natural Killer Cells (eBook)

Front cover 1
Natural killer cells: Basic Science and Clinical Application 4
Copyright page 5
Contents 6
Contributors 10
Foreword 14
Preface 20
PART I: NK biology 24
Chapter 1 Developmental stages and pathways of NK cell maturation 26
The early events in hematopoiesis 26
NK cells as a distinct cell type 27
Lineage specific growth factors 27
Sites of NK development: the importance of the developmental environment 28
Fate determining interactions with stroma 29
Transcription factors involved in NK cell differentiation 30
Second messenger signalling in NK cell development 33
The NK cell ontogeny—lessons from evolution 34
Lessons from embryogenesis 35
Lessons from NK cell immune reconstitution after hematopoietic cell transplantation 35
Stages of NK cell development 36
Acquisition of inhibitory receptors during NK cell development 37
Linear and branching models of human NK cell development 38
Boundaries of NK cell lineage 39
Summary 40
Chapter 2 Developmental origins of thymus-derived natural killer cells 48
Introduction 48
Fetal thymic NK cell ontogeny 49
Early thymus-independent stages of fetal NK cell development 51
Dispelling the NK1.1 expression myth: NKR-P1B precedes NKR-P1C during NK lineage specification 51
NK-lineage specification versus commitment 52
NK1.1[sup(+)]CD117[sup(+)]CD90[sup(+)] precursors and their relationship to thymic NK cells 54
NK cell development in vivo: developmental stages versus subsets of differentiation 55
Composite phenotype of fetal versus adult thymic NK cells 57
TNK cells: physiological bipotent progenitor or lymphoid tissue inducer (LTi)-like cell? 58
Concluding remarks 58
Acknowledgements 59
References 59
Chapter 3 Interferon-producing killer dendritic cells (IKDC) 64
NK antigen-presenting cells 65
Interferon-producing killer dendritic cells 65
IKDC, a unique link between innate and adaptive immunity 71
Translational implications and concluding remarks 73
References 74
Chapter 4 Natural killer cells in cancer 78
Introduction 78
NK cells in the host response against tumours 78
Treating patients with adoptive transfer of NK cells 82
Acknowledgements 84
References 84
Chapter 5 NK cell immune recognition: NKG2D ligands and stressed cells 88
Introduction 88
NKG2D receptor 89
NKG2D ligand family members: structure and function 90
NKG2D ligands are inducible: role in cancer 92
Tumour immune evasion 92
Role of NKG2D in infection 93
NKG2D and disease 95
NKG2D in graft and transplantation 96
Acknowledgement 96
References 97
Chapter 6 NK cell KIR heterogeneity and evolution 102
The roles of MHC class I inhibitory receptors in NK cell function 103
Human KIR variation 103
Human NK cell repertoires 109
NK cell heterogeneity as a common feature in mammalian NK cell systems 112
Impact of KIR diversity on human health and disease 112
References 113
Chapter 7 Signalling events in natural killer cells 118
Introduction 118
Inhibitory NK receptors 119
Activating NK receptors 120
Signalling for NK-cell recruitment 126
Signals involved in NK-mediated immunoediting 129
References 131
Chapter 8 Human natural killer cell development 136
Introduction 136
Stages of human NK development 137
The location of human NK development 137
Diversity in development and function 139
Cytokines driving development 140
Gene regulation of NK cell development 140
NK education and regulation beyond final maturation 142
Conclusion 143
Acknowledgements 143
References 143
PART II: NK interactions with other cells 146
Chapter 9 Isolation, culture and propagation of natural killer cells 148
Introduction 148
Isolation of NK cells 149
Activation and expansion of NK cells 153
Conclusions 156
Financial support 157
References 157
Chapter 10 The localization and migration of natural killer cells in health and disease 160
Introduction 160
NK cells in secondary lymphoid organs 161
NK cells in other organs 163
NK cell migration 166
Do NK cells traffic? 170
Concluding remarks 171
References 171
Chapter 11 Receptors on NK cells 178
Inhibitory NK receptors 179
Activating NK receptors 183
Summary 188
References 188
Chapter 12 Development and testing of NK cell lines 192
Establishing an NK cell line as a clinical-grade product 193
Targeting of NK cell lines to tumours 196
Transfecting IL-2 and FcR into NK cell lines 196
References 197
Chapter 13 NK cell-derived cytokines and delivery: NK cell synapses 200
Cytokine production by NK cell subsets 200
Cytokine secretion pattern of decidual NK cells 201
Stimuli inducing cytokine secretion by NK cells 202
The NK cell immune synapse 203
NK–DC synapse 204
DC-mediated NK cell activation 205
NK cell-mediated DC activation 207
References 208
Chapter 14 NK cells as recipients of cytokine signals 212
Introduction 212
Cells influencing NK behaviour 213
Cytokines that affect NK cells 213
Other cytokine effects 219
Effector signalling pathways 219
Conclusion 220
References 220
Chapter 15 NK cells and chemokines 226
Introduction 226
Chemokine receptor expression by NK cells and chemokine-regulated NK cell functions in vitro 228
Signalling events controlling chemokine-regulated NK cell functions 230
In vivo regulation of NK cell functions by chemokines 231
Conclusions 233
Acknowledgements 233
References 234
Chapter 16 Natural killer cytolytic activity 238
Introduction 238
NK cell subsets and localization 239
Granule exocytosis model overview 239
Lytic granule components 240
Pore delivery model 243
Consequences of perforin deficiency 243
Granzyme-deficient mice 245
Death-receptor mediated cytotoxicity 245
Immunological consequences of NK cytotoxicity 246
References 247
Chapter 17 Illuminating intranodal natural killer cell behaviour using two-photon microscopy 252
NK cell development and tissue distribution 252
NK cell recruitment to LN 253
NK cell distribution within LN 253
Imaging intranodal NK cell dynamics 255
Cognate NK–target cell interactions 256
Imaging NK–DC interactions 257
Concluding remarks 258
Acknowledgements 258
References 258
Chapter 18 Dendritic cells and NK cells 262
Dendritic cells: the professional antigen-presenting cell 263
DC heterogeneity and hematopoietic development 265
DCs: lymphoid and/or myeloid origin? 265
Functional niches for DC subsets 266
Direct instructions from pathogens: DC activation through PRRs 266
Indirect instructions: DC activation through endogenous 'danger' signals 266
Killer DCs: another function for DCs 267
DC activation of NK cells through cell-to-cell contact 267
DC activation of NK cells by soluble factors 268
Role of killer effector cells in determining DC-mediated polarized immune responses 269
Reverse 'help' from NK cells 269
DC: NK crosstalk in peripheral tissues 269
DC–NK crosstalk in lymph nodes 270
Exploiting NK 'helper'/DC1 driving function in cancer 270
References 272
Chapter 19 NK and NKT cells: the innate–adaptive interface including humoral responses 278
Introduction 278
Functions of NK cells 279
Conclusions regarding the role of NK cells in regulating adaptive immune responses 285
NKT cells 286
NKT cell characterization, tissue and species distribution 286
NKT cell development 287
NKT cell mechanisms of action 288
CD1d regulates NKT cell tolerance and pathogenesis 289
Functional subsets of NKT cells 291
Conclusion 292
References 293
Chapter 20 NK cell and endothelial cell interactions 302
NK cell tissue distribution 302
Conclusion 308
Acknowledgements 309
References 309
Chapter 21 Natural killer cell/epithelial interactions 312
Phenotype of NK cells 312
Chemokine receptors of NK Cell 313
Adhesion molecules on NK cells 313
NK cell distribution and characteristics in normal skin in mouse and human 313
Abnormalities in NK cell distribution, activity and number in inflamed skin 314
NK cell–keratinocyte interactions 314
The role of NK cells in psoriasis 314
NK cells and allergic contact hypersensitivity 315
NK cells and the hair follicle epithelium in health and disease 315
Epithelium of the kidney and NK cells 316
Waldeyer's ring and NK cells 316
Airway epithelial cells and NK cells 316
Conclusions 317
References 317
Chapter 22 NK cell–T cell interactions 320
Introduction 320
T lymphocyte populations 321
NK cell populations 321
NK cell cytokine production and T cell activation 322
NK cells as antigen-presenting cells 323
NK cell-mediated killing as a means of controlling T cell responses 324
T cell effects on NK cells 325
Conclusion 326
Acknowledgements 326
References 326
PART III: NK cells in the tissues 332
Chapter 23 NK cells and NKT cells in cutaneous disorders 334
Introduction 334
Allergic contact dermatitis 336
Psoriasis 337
Atopic dermatitis 338
UV-induced cutaneous immune suppression 339
Cutaneous lymphomas 340
Conclusions 340
References 341
Chapter 24 Natural killer cells in the respiratory tract 344
Introduction 344
Cancer 345
Infectious diseases 345
Other inflammatory lung diseases 348
References 349
Chapter 25 Intestinal natural killer cells 354
Introduction 354
Identification of cytotoxic NK cells in the small and large intestine 355
Studies on human intestinal epithelial lymphocytes 355
Studies on human lamina propria lymphocytes 356
An NKp44[sup(+)] NK cell population in the human gut 356
Animal studies 357
Rat intestinal NK cells 357
NK cells in the amphibian and avian gut 358
Origins of NK cells in intestinal tissue 358
NK lymphoid progenitor cells in the gut 358
Alternative role for NK cells in 'wound healing' in intestinal tissues 359
Commensal microflora and pathways to activation of NK cells in the healthy intestine 360
Intestinal NK cells and enteric pathogens 361
Human immunodeficiency virus (HIV) infection and intestinal NK cells 361
Conclusions 364
References 364
Chapter 26 Natural killer cells in the liver 368
Introduction 368
Location of NK cells in the liver 369
Development of liver NK cells 369
References 375
Chapter 27 Natural killer cells in the spleen and lymph node 382
Introduction 382
Homing of lymphocytes to the LN at steady state 383
Homing of lymphocytes to the spleen at steady state 384
Lymphocyte migration within spleen and LN T-cell areas at steady state 384
NK cells in LN and spleen T-cell areas at steady state 385
Spleen and LNs in NK cell development and homeostasis 385
Regulatory role of CD4[sup(+)]CD25[sup(+)]Foxp3[sup(+)] T cells in NK cell activation in the LN in steady state 386
The inflamed LN and spleen 387
NK cell recruitment to the inflamed LN and spleen 387
Recruitment of circulating NK cells to inflamed LN and spleen T-cell areas is CXCR3-dependent 388
Activated and immigrating DCs as the potential source of CXCL3-ligands 389
Induced recruitment of NK cells to an inflamed LN provides IFN-gamma for T[sub(H)]1 priming 389
DC-mediated priming of NK cells leads to effector NK cell release into the circulation 390
References 391
Chapter 28 Nature killer cells in the central nervous system 396
Homing of NK cells into the CNS 396
NK cell-mediated neuron, oligodendrocyte and glial cell damage 397
NK cells in infection of the CNS 398
NK cells and tumour immune surveillance of the CNS 400
Regulatory functions of NK cells in CNS inflammation and autoimmunity 402
Summary and future research directions 403
Acknowledgements 404
References 404
Chapter 29 NK cells in the eye 408
Introduction 408
Immune privilege of the eye 409
Anatomical and structural properties of the eye that limit immune-mediated responses 410
Anti-inflammatory and immunosuppressive soluble factors in the eye 411
Cell membrane-bound factors that contribute to immune privilege 411
ACAID: A dynamic immunoregulatory process that sustains immune privilege in the eye 412
Ocular immune privilege and NK cells 413
Role of NK cells in bacterial, viral and neoplastic diseases of the eye 413
Conclusions 419
References 419
Chapter 30 NK cells and reproduction 426
Introduction 426
History and terminology 427
Uterine NK cells and the menstrual cycle 428
The origin of uterine NK cells 429
Phenotype of uterine NK cells 429
Function of uterine NK cells 431
Potential ligands for NK cells on trophoblast 433
Concluding remarks 436
References 436
Chapter 31 Identification of natural killer cells in tissues and their isolation 440
Introduction 440
NK cell subsets 441
NK cells in normal tissues 442
NK cells in disease 446
References 451
Chapter 32 Natural killer cell immune regulation: coordination of immune function in tissues 456
Introduction 456
Cellular interactions in innate immune responses 457
NK cell activation at inflammatory sites: role of receptor–ligand interactions and of TLRs 457
NK–DC interactions: NK cell-mediated killing of immature myeloid DCs (DC 'editing') 458
NK cell-promoted maturation of myeloid DCs 458
Role of cytokine microenvironment in the modulation of innate and adaptive immune responses 459
NK cell interactions with mast cells: regulatory effects on the innate immunity 459
NK cells interaction with PDCs 461
Conclusions 461
Acknowledgements 462
References 462
PART IV: NK cells in disease 466
Chapter 33 Natural killer cells and transplantation 468
Introduction 468
Heart transplantation 469
Lung transplantation 470
Small bowel transplantation 471
Liver transplantation 471
Kidney transplantation 471
Skin transplantation 472
Pancreatic islet transplantation 473
Xenotransplantation 473
Chemokine-directed NK cell allograft infiltration 474
Transplantation immunotherapies and NK cell function 475
Conclusions 478
References 478
Chapter 34 Natural killer cells and autoimmunity 484
Introduction 484
Genetic association of NK cell receptor variation with autoimmune disease 485
Functional characteristics and models of NK cells in autoimmune diseases 485
Influence of NK cells on autoimmune T cell polarization 486
NK cell editing of myeloid cells 487
Direct targeting of autoimmune lymphocytes by NK cells 487
Summary 488
Acknowledgements 488
References 488
Chapter 35 Interaction of NK cells with bacteria 492
Introduction 492
Host defence by NK cells 493
Recognition of pathogens by PRRs 493
Crosstalk between NK cells and DCs 494
Regulation of Th1 immunity by lactic acid bacteria 494
The mechanism of NK and NKT activation by glycolipid & #945
NKT cells act as regulatory cells rather than killer cells during activation of NK cell-mediated cytotoxicity by& #945
Application of immunological theory to cancer immunotherapy and activation of innate immunity for cancer therapy 498
Activation of acquired immunity for cancer therapy using bacterial adjuvants 498
Conclusions 499
References 500
Chapter 36 Natural killer cells and human immunodeficiency virus 504
Introduction 505
Infection of NK cells by HIV-1 505
Effect of HIV-1 viraemia on NK cells 506
Interactions between NK cells and autologous DCs in HIV-1 infection 512
Effect of ART on NK cell phenotype and functions 513
Modulation of NK cell effector function in response to cytokines during HIV-1 infection 513
NK cells and resistance to HIV-1 infection 514
Genetic factors associated with a positive NK cell-mediated clinical outcome of HIV-1 infection 515
Future perspective 516
Acknowledgements 517
References 517
Chapter 37 Cytomegalovirus infection and NK cells 522
Cytomegalovirus 522
The role of NK cells in CMV infection 523
NK cell activation in CMV infection 525
Viral evasion of NK cell responses 526
NK cells can regulate anti-viral adaptive immune responses 528
Conclusion and perspectives 529
References 531
Chapter 38 Natural killer cells in allergy 534
Pathogenesis of allergic disease 534
Regulatory role of NK cells in allergy 535
NK subsets with regulatory function 535
NK cells in the lymph node 536
NK–DC crosstalk in allergy 536
NK cells and T cells 536
NK cells and eosinophils 536
NK cells and asthma 537
NK cells and atopic dermatitis 537
Concluding remarks 538
References 538
Chapter 39 Natural killer cells in wound healing 542
Wound healing 542
Conclusions 547
Acknowledgements 547
References 547
Chapter 40 Natural killer cells in atherosclerosis 550
NK cells in murine atherosclerosis 551
Conclusion 554
Acknowledgements 554
References 554
Chapter 41 Natural killer cells in leukaemia 556
Introduction 556
NK cells as effectors of antileukaemia activity 557
NK cells in acute leukaemia 557
NK cells in chronic leukaemia 559
NK cells and CLL 560
NK cells in myelodysplasia 560
NK cells in chronic myeloproliferative disorders 561
Immunotherapy 561
Conclusions 562
Acknowledgements 562
References 562
Chapter 42 Natural killer cells and allogeneic haematopoietic cell transplantation 566
Introduction 566
NK cell alloreactivity in allogeneic HCT: pre-clinical data 568
Donor-versus-recipient NK cell alloreactivity in allogeneic HCT 568
Guidelines for NK alloreactive donor selection 571
Another NK cell effect in transplantation: the missing ligand model 571
Do activating KIRs play a role in transplantation? 572
Conclusions 572
Acknowledgements 573
References 573
Chapter 43 Clinical trials of NK cells for cancer 578
Introduction 579
Biologic basis of NK cell-mediated therapies 579
Therapeutic applications for NK cells 581
Clinical-scale GMP production and expansion of human NK cells 585
Summary 588
References 589
Chapter 44 Natural killer cells and hepatitis C virus infection 594
Introduction 595
Hepatitis C virus 595
Host response to HCV infection 597
Current therapy of HCV infection 605
Acknowledgement 605
References 606
Chapter 45 Natural killer cells and the biology of parasitism 612
Introduction 612
Malaria 613
Toxoplasma gondii 615
Leishmaniasis 617
Trypansoma cruzi 618
Helminths 619
Conclusion 620
References 620
Chapter 46 Lymphoproliferative disorders of natural killer cells 624
Introduction 624
WHO recognized NK cell neoplasms 625
Inter-relation of the WHO recognized NK cell neoplasms 632
References 634
PART V: Special topics in NK biology 638
Chapter 47 Natural killer cell induction of tolerance 640
NK cell self-tolerance 641
Non-MHC-class-I–specific NK-cell recognition 644
NK cells in regulation of immune responses 645
References 651
Chapter 48 Genetic engineering of natural killer cells 656
Introduction 656
Expression of transgenes by primary NK cells and NK cell lines 657
Adenoviral transduction of primary, IL-2-activated NK cells—marker genes 658
A-NK cell transduction—cytokine genes—IL-2 658
IL-12 gene transduction enhances IFN[sub(& #947
Reduced need for exogenous IL-2 support by A-NK cells transduced to express IL-12 660
Superior antitumour effect by A-NK[sub(12)] cells compared to A-NK[sub(mock)] cells 661
Local IL-12 production benefits 'bystander' nontransduced A-NK cells 661
IL-12 induced host production of IFN[sub(& #947
Transduction of A-NK cells to express both IL-12 and TNF& #945
Simultaneous transduction of NK cells with IL-12 and IL-2 genes eliminates the need for exogenous IL-2 665
Promising outlook for genetically engineered NK cells 665
References 666
Chapter 49 NK cell-mediated target cell death 668
Introduction 668
Cell-mediated cytotoxicity 669
Death-associated proteolytic activities in target cells as a measure of effector cell lethality 671
Antibody-dependent cellular cytotoxicity 672
Conclusions 673
References 673
Chapter 50 NK-cell tracking using non-invasive imaging modalities 676
Introduction 676
Routes for NK-cell administration 678
Imaging techniques for tracking of NK cells 678
Optical imaging for tracking of NK-cell immunotherapy 679
MR imaging 680
NK cell tracking with bifunctional contrast agents or double labelling techniques 683
FDG-PET imaging 683
Other radiotracer modalities 684
Translational and clinical applications 684
Conclusion 684
References 685
Subject index 688
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Colour plates section 702