Natural killer cells : basic science and clinical application

Copyright......Page 1
Contributors......Page 2
Foreword......Page 6
Preface......Page 11
The early events in hematopoiesis......Page 14
Lineage specific growth factors......Page 15
Sites of NK development: the importance of the developmental environment......Page 16
Fate determining interactions with stroma......Page 17
Transcription factors involved in NK cell differentiation......Page 18
Second messenger signalling in NK cell development......Page 21
The NK cell ontogeny—lessons from evolution......Page 22
Lessons from NK cell immune reconstitution after hematopoietic cell transplantation......Page 23
Stages of NK cell development......Page 24
Acquisition of inhibitory receptors during NK cell development......Page 25
Linear and branching models of human NK cell development......Page 26
Boundaries of NK cell lineage......Page 27
Summary......Page 28
Introduction......Page 36
Fetal thymic NK cell ontogeny......Page 37
Dispelling the NK1.1 expression myth: NKR-P1B precedes NKR-P1C during NK lineage specification......Page 39
NK-lineage specification versus commitment......Page 40
NK1.1+CD117+CD90+ precursors and their relationship to thymic NK cells......Page 42
NK cell development in vivo: developmental stages versus subsets of differentiation......Page 43
Composite phenotype of fetal versus adult thymic NK cells......Page 45
Concluding remarks......Page 46
Acknowledgements......Page 47
Interferon-producing killer dendritic cells (IKDC)......Page 51
Interferon-producing killer dendritic cells......Page 52
Isolation and molecular characterization......Page 53
IKDCs are ‘multi-talented’ cells endowed with NK and DC functions......Page 55
Antigen-presenting function of IKDC......Page 57
IKDC, a unique link between innate and adaptive immunity......Page 58
Translational implications and concluding remarks......Page 60
Cytokine secretion: IKDCs simultaneously produce IFNs and IL-12......Page 56
NK cells in the host response against tumours......Page 65
The early days—towards an understanding of NK cell tumour recognition......Page 66
NK cell receptors involved in human tumour recognition......Page 67
NK cell targeting of primary human tumour cells......Page 68
Treating patients with adoptive transfer of NK cells......Page 69
Acknowledgements......Page 71
Introduction......Page 75
NKG2D receptor......Page 76
NKG2D ligand family members: structure and function......Page 77
Tumour immune evasion......Page 79
Role of NKG2D in infection......Page 80
NKG2D and disease......Page 82
Acknowledgement......Page 83
NK cell KIR heterogeneity and evolution......Page 88
Human KIR variation......Page 89
Gene content variation and the A- and B-haplotypes......Page 90
KIR allotype functions and allele-level haplotypes......Page 92
Genetic determinants of diverse NK subset responses against missing-self......Page 95
Effect of HLA class I ligands on KIR expression......Page 96
Classifying diverse human NK cell repertoires into five groups......Page 97
Impact of KIR diversity on human health and disease......Page 98
Introduction......Page 104
Inhibitory NK receptors......Page 105
Activating NK receptors......Page 106
NKG2-family of C-lectin-like receptors......Page 107
Natural cytotoxicity receptors (NCR)......Page 109
Transcriptional NK receptor control......Page 110
Signals that mediate lytic granule mobilization......Page 112
NK receptor signalling in T-cells......Page 114
Signals involved in NK-mediated immunoediting......Page 115
Bi-directional cross-talk......Page 116
Introduction......Page 122
The location of human NK development......Page 123
Diversity in development and function......Page 125
Gene regulation of NK cell development......Page 126
NK education and regulation beyond final maturation......Page 128
Acknowledgements......Page 129
Introduction......Page 132
Percoll density gradient centrifugation......Page 133
Flow cytometric analysis......Page 134
Preparation of single cell suspension of viable splenocytes......Page 135
Testing purity of NK cells......Page 136
Activation and expansion of NK cells......Page 137
Selection of A-NK cells......Page 138
Activation and culture of purified fresh whole population of NK cells......Page 139
Conclusions......Page 140
Financial support......Page 141
Introduction......Page 143
Lymph node NK cells......Page 144
Splenic NK cells......Page 145
NK cells in other organs......Page 146
Liver NK cells......Page 147
Thymic NK cells......Page 148
CC chemokines......Page 149
CXC chemokines......Page 151
Do NK cells traffic?......Page 153
Concluding remarks......Page 154
Receptors on NK cells......Page 160
MHC class I-mediated inhibition......Page 161
Leukocyte Ig-like inhibitory receptors......Page 162
Carcinoembryonic antigen-related cell adhesion molecule 1......Page 163
Sialic-acid-binding immunoglobulin-like lectins......Page 164
NKG2D......Page 165
NKp46......Page 167
NKp80......Page 168
DNAM-1......Page 169
Summary......Page 170
Development and testing of NK cell lines......Page 174
Establishing an NK cell line as a clinical-grade product......Page 175
Transfecting IL-2 and FcR into NK cell lines......Page 178
References......Page 179
Cytokine production by NK cell subsets......Page 181
Cytokine secretion pattern of decidual NK cells......Page 182
TLR ligands......Page 183
Activating NK-IS......Page 184
NK–DC synapse......Page 185
DC-mediated NK cell activation......Page 186
IL-18......Page 187
NK cell-mediated DC activation......Page 188
Introduction......Page 193
Cytokines that affect NK cells......Page 194
IL-12......Page 195
IL-21......Page 196
Chemokines......Page 197
CX3CL1/CX3CR1......Page 198
Other chemokines......Page 199
Other important signalling components......Page 200
Conclusion......Page 201
Introduction......Page 206
Chemokine receptor expression by NK cells and chemokine-regulated NK cell functions in vitro......Page 208
Signalling events controlling chemokine-regulated NK cell functions......Page 210
In vivo regulation of NK cell functions by chemokines......Page 211
Acknowledgements......Page 213
Introduction......Page 217
Granule exocytosis model overview......Page 218
Perforin......Page 219
Granzymes......Page 220
Serglycin......Page 221
Consequences of perforin deficiency......Page 222
Perforin and viral infection......Page 223
Death-receptor mediated cytotoxicity......Page 224
Immunological consequences of NK cytotoxicity......Page 225
NK cell development and tissue distribution......Page 230
NK cell distribution within LN......Page 231
Principles of two-photon immunoimaging......Page 232
Imaging intranodal NK cell dynamics......Page 233
Cognate NK–target cell interactions......Page 234
Imaging NK–DC interactions......Page 235
Acknowledgements......Page 236
Dendritic cells and NK cells......Page 239
Dendritic cells: the professional antigen-presenting cell......Page 240
Decision making by DCs......Page 241
DCs: lymphoid and/or myeloid origin?......Page 242
Indirect instructions: DC activation through endogenous ‘danger’ signals......Page 243
DC activation of NK cells through cell-to-cell contact......Page 244
DC activation of NK cells by soluble factors......Page 245
DC: NK crosstalk in peripheral tissues......Page 246
Exploiting NK ‘helper’/DC1 driving function in cancer......Page 247
Introduction......Page 254
NK receptors......Page 255
The role of NK cells at the innate-adaptive interface......Page 257
NK cells in cancer......Page 258
NK cells in autoimmunity......Page 259
Role of NK cells in primary B cell responses......Page 260
Conclusions regarding the role of NK cells in regulating adaptive immune responses......Page 261
NKT cell characterization, tissue and species distribution......Page 262
NKT cell development......Page 263
NKT cell effector functions......Page 264
CD1d regulates NKT cell tolerance and pathogenesis......Page 265
Functional subsets of NKT cells......Page 267
Conclusion......Page 268
NK cell tissue distribution......Page 277
Adhesion molecules involved in the control of NK cell–endothelial cell interactions......Page 278
Integrins......Page 279
NK cell-mediated promotion of vascular remodelling......Page 281
NK cell-mediated endothelial cell damage and anti-angiogenic effects......Page 282
Conclusion......Page 283
Acknowledgements......Page 284
Phenotype of NK cells......Page 287
NK cell distribution and characteristics in normal skin in mouse and human......Page 288
The role of NK cells in psoriasis......Page 289
NK cells and the hair follicle epithelium in health and disease......Page 290
Airway epithelial cells and NK cells......Page 291
Conclusions......Page 292
Introduction......Page 295
NK cell populations......Page 296
NK cell cytokine production and T cell activation......Page 297
NK cells as antigen-presenting cells......Page 298
NK cell-mediated killing as a means of controlling T cell responses......Page 299
T cell effects on NK cells......Page 300
Acknowledgements......Page 301
Biology of NK cells......Page 307
The history of NKT cell discovery......Page 308
NKT cells......Page 309
Psoriasis......Page 310
Atopic dermatitis......Page 311
NKT cells......Page 312
Conclusions......Page 313
Introduction......Page 317
Infectious diseases......Page 318
Viral infections......Page 319
Bacterial infections......Page 320
Other inflammatory lung diseases......Page 321
Introduction......Page 326
Studies on human intestinal epithelial lymphocytes......Page 327
An NKp44 NK cell population in the human gut......Page 328
Rat intestinal NK cells......Page 329
NK lymphoid progenitor cells in the gut......Page 330
Alternative role for NK cells in ‘wound healing’ in intestinal tissues......Page 331
Commensal microflora and pathways to activation of NK cells in the healthy intestine......Page 332
Inflammatory bowel diseases and celiac disease; NK cell involvement?......Page 333
Conclusions......Page 336
Introduction......Page 340
Development of liver NK cells......Page 341
Cytotoxicity of liver NK cells......Page 342
NK cells and viral infection in the liver......Page 343
NK cells in liver cancer......Page 344
Liver NK cells and hepatic tolerance......Page 345
NK cells in liver fibrosis......Page 346
Liver NK cells as a bridge between innate and adaptive immunity......Page 347
Introduction......Page 353
Homing of lymphocytes to the LN at steady state......Page 354
Lymphocyte migration within spleen and LN T-cell areas at steady state......Page 355
Spleen and LNs in NK cell development and homeostasis......Page 356
Regulatory role of CD4+CD25+Foxp3+ T cells in NK cell activation in the LN in steady state......Page 357
NK cell recruitment to the inflamed LN and spleen......Page 358
Recruitment of circulating NK cells to inflamed LN and spleen T-cell areas is CXCR3-dependent......Page 359
Induced recruitment of NK cells to an inflamed LN provides IFN-gamma for TH1 priming......Page 360
DC-mediated priming of NK cells leads to effector NK cell release into the circulation......Page 361
Homing of NK cells into the CNS......Page 367
Neuron......Page 368
NK cells in infection of the CNS......Page 369
Semliki Forest virus......Page 370
NK cells and tumour immune surveillance of the CNS......Page 371
Other CNS tumours......Page 372
Regulatory functions of NK cells in CNS inflammation and autoimmunity......Page 373
Summary and future research directions......Page 374
Acknowledgements......Page 375
Introduction......Page 378
Immune privilege of the eye......Page 379
Anatomical and structural properties of the eye that limit immune-mediated responses......Page 380
Cell membrane-bound factors that contribute to immune privilege......Page 381
Thymic phase of ACAID......Page 382
Herpes simplex virus keratitis......Page 383
Pseudomonas keratitis......Page 384
Corneal allograft rejection......Page 385
Uveitis......Page 386
Uveal melanoma......Page 387
Conclusions......Page 389
Introduction......Page 395
History and terminology......Page 396
Uterine NK cells and the menstrual cycle......Page 397
Phenotype of uterine NK cells......Page 398
Function of uterine NK cells......Page 400
Maintenance and modification of the vasculature......Page 401
Potential ligands for NK cells on trophoblast......Page 402
HLA-C......Page 403
HLA-G......Page 404
Concluding remarks......Page 405
Introduction......Page 409
NK cell subsets......Page 410
Lymphoid tissues......Page 411
Uterus......Page 412
Epithelia and lymphoid tissue-associated mucosae......Page 413
Other organs......Page 414
NK cells in disease......Page 415
NK cells in solid cancer......Page 417
Introduction......Page 424
NK cell activation at inflammatory sites: role of receptor–ligand interactions and of TLRs......Page 425
NK cell-promoted maturation of myeloid DCs......Page 426
NK cell interactions with mast cells: regulatory effects on the innate immunity......Page 427
Conclusions......Page 429
Acknowledgements......Page 430
Introduction......Page 433
Heart transplantation......Page 434
Lung transplantation......Page 435
Kidney transplantation......Page 436
Skin transplantation......Page 437
Xenotransplantation......Page 438
Chemokine-directed NK cell allograft infiltration......Page 439
Transplantation immunotherapies and NK cell function......Page 440
Conclusions......Page 443
Introduction......Page 448
Functional characteristics and models of NK cells in autoimmune diseases......Page 449
Influence of NK cells on autoimmune T cell polarization......Page 450
Direct targeting of autoimmune lymphocytes by NK cells......Page 451
Acknowledgements......Page 452
Introduction......Page 455
Recognition of pathogens by PRRs......Page 456
Regulation of Th1 immunity by lactic acid bacteria......Page 457
NKT cells act as regulatory cells rather than killer cells during activation of NK cell-mediated cytotoxicity by ?-GalCer in vivo......Page 459
Activation of acquired immunity for cancer therapy using bacterial adjuvants......Page 461
Conclusions......Page 462
Natural killer cells and human immunodeficiency virus......Page 467
Infection of NK cells by HIV-1......Page 468
Dichotomy in expression and function of iNKRs and NCRs......Page 469
NK cell-mediated killing of HIV-1 infected cells......Page 473
Antibody-dependent cell cytotoxicity......Page 474
Interactions between NK cells and autologous DCs in HIV-1 infection......Page 475
Modulation of NK cell effector function in response to cytokines during HIV-1 infection......Page 476
NK cells and resistance to HIV-1 infection......Page 477
Genetic factors associated with a positive NK cell-mediated clinical outcome of HIV-1 infection......Page 478
Therapeutic perspective......Page 479
Acknowledgements......Page 480
Cytomegalovirus......Page 484
The role of NK cells in CMV infection......Page 485
NK cell activation in CMV infection......Page 487
Altering the expression of MHC class I molecules......Page 488
NK cells can regulate anti-viral adaptive immune responses......Page 490
Conclusion and perspectives......Page 491
Pathogenesis of allergic disease......Page 496
NK subsets with regulatory function......Page 497
NK cells and eosinophils......Page 498
NK cells and atopic dermatitis......Page 499
Concluding remarks......Page 500
Wound healing......Page 503
Hemostasis and inflammation......Page 504
Re-epithelialization and granulation tissue formation......Page 505
Immunoregulatory NK cells in inflammation and tissue repair......Page 506
References......Page 508
NK cells in murine atherosclerosis......Page 511
Contribution of T cells and B cells......Page 512
Granzyme A promoter systems......Page 513
Acknowledgements......Page 514
Natural killer cells in atherosclerosis......Page 510
Introduction......Page 515
NK cells in acute leukaemia......Page 516
Activating receptors and AML......Page 517
NK cells in chronic leukaemia......Page 518
NK cells in myelodysplasia......Page 519
Antibodies......Page 520
Acknowledgements......Page 521
Introduction......Page 524
Donor-versus-recipient NK cell alloreactivity in allogeneic HCT......Page 526
Another NK cell effect in transplantation: the missing ligand model......Page 529
Conclusions......Page 530
Acknowledgements......Page 531
Clinical trials of NK cells for cancer......Page 535
NK cell functions: cytokine production and cytotoxicity......Page 536
NK cell alloreactivity: class I-recognizing inhibitory NK cell receptors and ‘missing self’......Page 537
Allogeneic NK cell therapy: biologic rationale......Page 538
Determination of NK cell alloreactivity......Page 539
Allogeneic NK cell therapy: hematopoietic cell transplantation......Page 540
Adoptive transfer of NK cells......Page 541
Clinical-scale GMP production and expansion of human NK cells......Page 542
Optimizing NK cell expansion: in vivo or ex vivo?......Page 543
Production of therapeutic NK cell line products......Page 544
Summary......Page 545
Natural killer cells and hepatitis C virus infection......Page 551
HCV proteins and structure......Page 552
Life cycle of HCV......Page 553
Hepatocyte infection, IFN production and HCV countermeasures......Page 554
NK cell receptors and HCV infection......Page 555
Class Ia HLA and killer cell immunoglobulin-like receptors (KIR)......Page 557
HLA class Ib and NK cells......Page 558
Interactions and crosstalk between NK cells and DC in the presence of HCV......Page 559
IL-15......Page 560
Other chemokines......Page 561
Acknowledgement......Page 562
Introduction......Page 568
Malaria......Page 569
Toxoplasma gondii......Page 571
Leishmaniasis......Page 573
Trypansoma cruzi......Page 574
Helminths......Page 575
Conclusion......Page 576
Introduction......Page 580
WHO recognized NK cell neoplasms......Page 581
Aggressive NK cell leukaemia......Page 585
Extranodal NK/T cell lymphoma, nasal type......Page 586
Inter-relation of the WHO recognized NK cell neoplasms......Page 588
Natural killer cell induction of tolerance......Page 593
Inhibitory receptors that recognize MHC class I molecules......Page 594
Challenges to ‘missing self’ recognition hypothesis......Page 595
Non-MHC-class-I–specific inhibitory receptors......Page 597
NK and dendritic cell interaction......Page 598
NK cells in transplantation......Page 600
NK cell tolerance and viral infection......Page 601
NK cells and maternal tolerance......Page 602
Breaking NK cell tolerance for cancer therapy......Page 603
Introduction......Page 608
Expression of transgenes by primary NK cells and NK cell lines......Page 609
A-NK cell transduction—cytokine genes—IL-2......Page 610
IL-12 gene transduction enhances IFN? production and CD25 expression by NK cells......Page 611
Reduced need for exogenous IL-2 support by A-NK cells transduced to express IL-12......Page 612
Local IL-12 production benefits ‘bystander’ nontransduced A-NK cells......Page 613
IL-12 induced host production of IFN? is essential for the antitumour effects of A-NK12 cells......Page 615
Transduction of A-NK cells to express both IL-12 and TNF?......Page 616
Promising outlook for genetically engineered NK cells......Page 617
Introduction......Page 620
Cell-mediated cytotoxicity......Page 621
Death-associated proteolytic activities in target cells as a measure of effector cell lethality......Page 623
Antibody-dependent cellular cytotoxicity......Page 624
Conclusions......Page 625
Introduction......Page 628
Imaging techniques for tracking of NK cells......Page 630
Techniques for NK-cell labelling with fluorochromes......Page 631
MR imaging......Page 632
Cell labelling for MR imaging......Page 633
In vivo imaging......Page 634
FDG-PET imaging......Page 635
Conclusion......Page 636
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