Functional significance of the perforin/granzyme cell death pathway

Immunobiology of Dendritic Cells

2000 • 6,653 citations

The Fas Death Factor

1995 • 4,070 citations

IFNγ and lymphocytes prevent primary tumour development and shape tumour immunogenicity

2001 • 2,658 citations

Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice

1994 • 1,772 citations

Generalized lymphoproliferative disease in mice, caused by a point mutation in the fas ligand

1994 • 1,549 citations

Perforin Gene Defects in Familial Hemophagocytic Lymphohistiocytosis

1999 • 1,212 citations

An Antimicrobial Activity of Cytolytic T Cells Mediated by Granulysin

1998 • 1,019 citations

Regulation of Cutaneous Malignancy by γδ T Cells

2001 • 945 citations

Cytotoxic T lymphocytes: all roads lead to death

2002 • 893 citations

HIV-Specific Cd8+ T Cells Produce Antiviral Cytokines but Are Impaired in Cytolytic Function

2000 • 879 citations

NKT cells: facts, functions and fallacies

2000 • 875 citations

Cytotoxic lymphocytes require granzyme B for the rapid induction of DNA fragmentation and apoptosis in allogeneic target cells

1994 • 844 citations

Differential Tumor Surveillance by Natural Killer (Nk) and Nkt Cells

2000 • 812 citations

Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells

2001 • 757 citations

Contact-dependent Stimulation and Inhibition of Dendritic Cells by Natural Killer Cells

2002 • 704 citations

Molecular Mechanisms of Lymphocyte-Mediated Cytotoxicity and Their Role in Immunological Protection and Pathogenesis In Vivo

1996 • 614 citations

Perforin-Mediated Cytotoxicity Is Critical for Surveillance of Spontaneous Lymphoma

2000 • 540 citations

Perforin and interferon-γ activities independently control tumor initiation, growth, and metastasis

2001 • 529 citations

Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (Trail) Contributes to Interferon γ–Dependent Natural Killer Cell Protection from Tumor Metastasis

2001 • 499 citations

Decreased tumor surveillance in perforin-deficient mice.

1996 • 487 citations

Immune function in mice lacking the perforin gene.

1994 • 474 citations

Regulation of Antigen-Specific CD8 ⁺ T Cell Homeostasis by Perforin and Interferon-γ

2000 • 452 citations

Purification of three cytotoxic lymphocyte granule serine proteases that induce apoptosis through distinct substrate and target cell interactions.

1992 • 447 citations

NK cells and NKT cells in innate defense against viral infections

2001 • 436 citations

T Cells Compete for Access to Antigen-Bearing Antigen-Presenting Cells

2000 • 423 citations

Granzymes: exogenous porteinases that induce target cell apoptosis

1995 • 403 citations

Mannose 6-Phosphate/Insulin-like Growth Factor II Receptor Is a Death Receptor for Granzyme B during Cytotoxic T Cell–Induced Apoptosis

2000 • 393 citations

Dipeptidyl peptidase I is required for the processing and activation of granzymes A and Bin vivo

1999 • 389 citations

A natural killer cell granule protein that induces DNA fragmentation and apoptosis.

1992 • 379 citations

Long-range disruption of gene expression by a selectable marker cassette

1996 • 377 citations

New Paradigm for Lymphocyte Granule-mediated Cytotoxicity

1996 • 368 citations

Initiation of Apoptosis by Granzyme B Requires Direct Cleavage of Bid, but Not Direct Granzyme B–Mediated Caspase Activation

2000 • 361 citations

Regulation of Experimental Autoimmune Encephalomyelitis by Natural Killer (NK) Cells

1997 • 360 citations

Pivotal role of phosphoinositide-3 kinase in regulation of cytotoxicity in natural killer cells

2000 • 348 citations

Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors

2001 • 347 citations

Distinct organ-dependent mechanisms for the control of murine cytomegalovirus infection by natural killer cells

1997 • 320 citations

Cytotoxic T cells deficient in both functional fas ligand and perforin show residual cytolytic activity yet lose their capacity to induce lethal acute graft-versus-host disease.

1996 • 310 citations

Elucidating the Autoimmune and Antitumor Effector Mechanisms of a Treatment Based on Cytotoxic T Lymphocyte Antigen-4 Blockade in Combination with a B16 Melanoma Vaccine

2001 • 307 citations

Granzyme B–Mediated Cytochrome C Release Is Regulated by the Bcl-2 Family Members Bid and Bax

2000 • 306 citations

Cytotoxic Cell Granule-Mediated Apoptosis

2002 • 297 citations

Perforin Is a Major Contributor to NK Cell Control of Tumor Metastasis

1999 • 290 citations

The roles of perforin‐ and Fas‐dependent cytotoxicity in protection against cytopathic and noncytopathic viruses

1995 • 286 citations

Not so Fas: Re-evaluating the mechanisms of immune privilege and tumor escape

2000 • 256 citations

Spectrum of Perforin Gene Mutations in Familial Hemophagocytic Lymphohistiocytosis

2001 • 253 citations

Defective Granule Exocytosis in Rab27a-Deficient Lymphocytes from Ashen Mice

2001 • 245 citations

Perforin expression in cytotoxic lymphocytes from patients with hemophagocytic lymphohistiocytosis and their family members

2002 • 244 citations

Role of Fas-mediated cell death in the regulation of immune responses

1996 • 243 citations

Granzyme A Loading Induces Rapid Cytolysis and a Novel Form of DNA Damage Independently of Caspase Activation

1999 • 238 citations

Target Cell Lysis by CTL Granule Exocytosis Is Independent of ICE/Ced-3 Family Proteases

1997 • 237 citations

Granzyme B (GraB) Autonomously Crosses the Cell Membrane and Perforin Initiates Apoptosis and GraB Nuclear Localization

1997 • 237 citations

Triggering of Natural Killer Cells by the Costimulatory Molecule CD80 (B7-1)

1996 • 233 citations

Reduced Incidence and Delayed Onset of Diabetes in Perforin-deficient Nonobese Diabetic Mice

1997 • 232 citations

T cells down-modulate peptide-MHC complexes on APCs in vivo

2001 • 227 citations

A Role for Perforin in Downregulating T-Cell Responses during Chronic Viral Infection

1999 • 227 citations

Surface Cathepsin B Protects Cytotoxic Lymphocytes from Self-destruction after Degranulation

2002 • 215 citations

Cytosolic Delivery of Granzyme B by Bacterial Toxins: Evidence that Endosomal Disruption, in Addition to Transmembrane Pore Formation, Is an Important Function of Perforin

1999 • 214 citations

Entry and Trafficking of Granzyme B in Target Cells During Granzyme B-Perforin–Mediated Apoptosis

1998 • 210 citations

Granzymes are the essential downstream effector molecules for the control of primary virus infections by cytolytic leukocytes

1999 • 207 citations

Expression of the Serpin Serine Protease Inhibitor 6 Protects Dendritic Cells from Cytotoxic T Lymphocyte–Induced Apoptosis

2001 • 205 citations

Differential use of Fas ligand and perforin cytotoxic pathways by donor T cells in graft-versus-host disease and graft-versus-leukemia effect

2001 • 187 citations

Granzyme A-deficient mice retain potent cell-mediated cytotoxicity.

1995 • 186 citations

A Central Role for Death Receptor-Mediated Apoptosis in the Rejection of Tumors by NK Cells

2001 • 185 citations

Granzymes A and B are targeted to the lytic granules of lymphocytes by the mannose-6-phosphate receptor.

1993 • 177 citations

Efficient Nuclear Targeting of Granzyme B and the Nuclear Consequences of Apoptosis Induced by Granzyme B and Perforin Are Caspase-dependent, but Cell Death Is Caspase-independent

1998 • 166 citations

Cytolytic pathways in haematopoietic stem-cell transplantation

2002 • 163 citations

Granzyme A Initiates an Alternative Pathway for Granule-Mediated Apoptosis

1999 • 163 citations

Bcl-2 prevents apoptosis induced by perforin and granzyme B, but not that mediated by whole cytotoxic lymphocytes.

1997 • 161 citations

Expression of the granzyme B inhibitor, protease inhibitor 9, by tumor cells in patients with non-Hodgkin and Hodgkin lymphoma: a novel protective mechanism for tumor cells to circumvent the immune system?

2002 • 156 citations

Granzyme B Induces BID-mediated Cytochrome c Release and Mitochondrial Permeability Transition

2001 • 155 citations

CD8+ Tumor-Infiltrating T Cells Are Deficient in Perforin-Mediated Cytolytic Activity Due to Defective Microtubule-Organizing Center Mobilization and Lytic Granule Exocytosis

2001 • 153 citations

Perforin-dependent NK cell cytotoxicity is sufficient for anti-metastatic effect of IL-12

1999 • 151 citations

A Distinct Pathway of Cell-Mediated Apoptosis Initiated by Granulysin

2001 • 151 citations

Homeostatic regulation of CD8+ T cells by perforin

1999 • 148 citations

Graft-Versus-Leukemia Effect and Graft-Versus-Host Disease Can Be Differentiated by Cytotoxic Mechanisms in a Murine Model of Allogeneic Bone Marrow Transplantation

1999 • 144 citations

Aplastic Anemia Rescued by Exhaustion of Cytokine-secreting CD8+ T Cells in Persistent Infection with Lymphocytic Choriomeningitis Virus

1998 • 142 citations

Granzyme A is critical for recovery of mice from infection with the natural cytopathic viral pathogen, ectromelia.

1996 • 139 citations

A view to a kill: signals triggering cytotoxicity.

2002 • 135 citations

Tumor-Specific CTL Kill Murine Renal Cancer Cells Using Both Perforin and Fas Ligand-Mediated Lysis In Vitro, But Cause Tumor Regression In Vivo in the Absence of Perforin

2002 • 128 citations

HSV and Glycoprotein J Inhibit Caspase Activation and Apoptosis Induced by Granzyme B or Fas

2001 • 120 citations

Perforin-independent β-cell destruction by diabetogenic CD8+ T lymphocytes in transgenic nonobese diabetic mice

1999 • 118 citations

Role of perforin in controlling B-cell hyperactivity and humoral autoimmunity

2000 • 115 citations

Granzyme B can cause mitochondrial depolarization and cell death in the absence of BID, BAX, and BAK

2001 • 113 citations

A Role of the Mitochondrial Apoptosis-Inducing Factor in Granulysin-Induced Apoptosis

2001 • 113 citations

Influence of effector molecules on the CD8+ T cell response to infection

2002 • 103 citations

Localization of Granzyme B in the Nucleus

1996 • 102 citations

Myelin oligodendrocyte glycoprotein‐induced autoimmune encephalomyelitis is chronic/relapsing in perforin knockout mice, but monophasic in Fas‐ and Fas ligand‐deficient lpr and gld mice

1997 • 101 citations

Lack of both Fas Ligand and Perforin Protects from Flavivirus-Mediated Encephalitis in Mice

2002 • 96 citations

Perforin Protects Against Autoimmunity in Lupus-Prone Mice

1998 • 95 citations

Perforin/Fas-Ligand Double Deficiency Is Associated with Macrophage Expansion and Severe Pancreatitis

1998 • 92 citations

CTL granules: evolution of vesicles essential for combating virus infections

1999 • 91 citations

Perforin Is Essential for Control of Ectromelia Virus but Not Related Poxviruses in Mice

1999 • 90 citations

Critical Role for Perforin-, Fas/FasL-, and TNFR1-Mediated Cytotoxic Pathways in Down-Regulation of Antigen-Specific T Cells during Persistent Viral Infection

2002 • 90 citations

Concerted Action of the FasL/Fas and Perforin/Granzyme A and B Pathways Is Mandatory for the Development of Early Viral Hepatitis but Not for Recovery from Viral Infection

2001 • 89 citations

Direct quantitation of rapid elimination of viral antigen-positive lymphocytes by antiviral CD8+ T cellsin vivo

2000 • 88 citations

Granzyme A and B-deficient killer lymphocytes are defective in eliciting DNA fragmentation but retain potentin vivo anti-tumor capacity

2001 • 87 citations

Immune evasion by tumours: involvement of the CD95 (APO-1/Fas) system and its clinical implications

1998 • 83 citations

Murine cytomegalovirus replication in salivary glands is controlled by both perforin and granzymes during acute infection

2000 • 82 citations

Perforin-mediated myocardial damage in acute myocarditis

1990 • 81 citations

Comparing the Relative Role of Perforin/Granzyme Versus Fas/Fas Ligand Cytotoxic Pathways in CD8+ T Cell-Mediated Insulin-Dependent Diabetes Mellitus

1999 • 78 citations

Compromised virus control and augmented perforin-mediated immunopathology in IFN-gamma-deficient mice infected with lymphocytic choriomeningitis virus.

1999 • 78 citations

Adenovirus L4-100K Assembly Protein Is a Granzyme B Substrate that Potently Inhibits Granzyme B-Mediated Cell Death

2001 • 78 citations

A Clonal Culture System Demonstrates That IL-4 Induces a Subpopulation of Noncytolytic T Cells with Low CD8, Perforin, and Granzyme Expression

2002 • 77 citations

Compromised Virus Control and Augmented Perforin-Mediated Immunopathology in IFN-γ-Deficient Mice Infected with Lymphocytic Choriomeningitis Virus

1999 • 74 citations

Papillon–Lefèvre Syndrome: Mutations and Polymorphisms in the Cathepsin C Gene

2001 • 72 citations

A Role for Perforin in Activation-Induced T Cell Death In Vivo: Increased Expansion of Allogeneic Perforin-Deficient T Cells in SCID mice

1999 • 72 citations

Perforin-independent regulation of dendritic cell homeostasis by CD8+ T cellsin vivo: implications for adaptive immunotherapy

2001 • 71 citations

A molecular genetic linkage map of mouse chromosome 19, including thelpr, Ly-44, andTdt genes

1991 • 68 citations

IL-4 Diminishes Perforin-Mediated and Increases Fas Ligand-Mediated Cytotoxicity In Vivo

2000 • 66 citations

Virally Infected Hepatocytes Are Resistant to Perforin-Dependent CTL Effector Mechanisms

2001 • 65 citations

Regulation of pro‐apoptotic leucocyte granule serine proteinases by intracellular serpins

1999 • 64 citations

The Relative Role of Lymphocyte Granule Exocytosis versus Death Receptor-Mediated Cytotoxicity in Viral Pathophysiology

1998 • 62 citations

L is for lytic granules: lysosomes that kill

1998 • 56 citations

Transgenic overexpression of human Bcl-2 in islet β cells inhibits apoptosis but does not prevent autoimmune destruction

2000 • 54 citations

A mouse CD8 T cell-mediated acute autoimmune diabetes independent of the perforin and Fas cytotoxic pathways: Possible role of membrane TNF

2000 • 54 citations

T Cell-Mediated Tumor Rejection Displays Diverse Dependence Upon Perforin and IFN-γ Mechanisms That Cannot Be Predicted From In Vitro T Cell Characteristics

2000 • 47 citations

Role of Effector Cell-Derived IL-4, IL-5, and Perforin in Early and Late Stages of Type 2 CD8 Effector Cell-Mediated Tumor Rejection

2001 • 46 citations

Structure, Function and Expression of Murine and Human Perforin 1 (P1)

1988 • 42 citations

Perforin- and Fas-dependent mechanisms of natural killer cell-mediated rejection of incompatible bone marrow cell grafts

2002 • 40 citations

Trypanosoma cruzi: Roles for Perforin-Dependent and Perforin-Independent Immune Mechanisms in Acute Resistance

2000 • 38 citations

Perforin Is Required for Primary Immunity toHistoplasma capsulatum

2001 • 34 citations

Poxvirus-Encoded Serpins Do Not Prevent Cytolytic T Cell-Mediated Recovery from Primary Infections

1999 • 34 citations

Pathogenesis of Herpes Simplex Virus Type 1-Induced Corneal Inflammation in Perforin-Deficient Mice

2000 • 33 citations

Enhanced susceptibility to Theiler's virus-induced demyelinating disease in perforin-deficient mice

2001 • 32 citations

Phosphatidylinositol 3-Kinase-Dependent and -Independent Cytolytic Effector Functions

1999 • 31 citations

Inhibition of the Death Receptor Pathway by cFLIP Confers Partial Engraftment of MHC Class I-Deficient Stem Cells and Reduces Tumor Clearance in Perforin-Deficient Mice

2001 • 20 citations

Epstein–Barr virus‐specific T‐cell cytotoxicity is mediated through the perforin pathway in patients with lymphoproliferative disorders after allogeneic bone marrow transplantation

2002 • 19 citations

Distinct CD8 T Cell Functions Mediate Susceptibility to Histoplasmosis During Chronic Viral Infection

2001 • 12 citations