Perforin and Fas killing by CD8+ T cells limits their cytokine synthesis and proliferation

During an immune response, effector CD8+ T cells can kill infected cells by the perforin-dependent pathway. In comparison to CD4+ T cells, which are major sources of cytokines, normal CD8+ T cells produced less interleukin 2 and interferon gamma, and proliferated less vigorously after antigenic stimulation. Killing of target cells was a major cause of these reduced responses, since perforin-deficient CD8+ T cells showed substantially increased cytokine synthesis and proliferation. Cytotoxicity by the alternate Fas pathway also resulted in self- limitation of CD8+ T cell cytokine synthesis. This relationship between cytotoxicity and cytokine synthesis may regulate CD8+ T function in different phases of an immune response.

• Publication year

  1996

• Venue

  Journal of Experimental Medicine

• Publication date

  1996-10-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1084/JEM.184.4.1543PMID 8879227PMCID 2192809
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Different responses are elicited in cytotoxic T lymphocytes by different levels of T cell receptor occupancy

  1996cited by this paper
• Immunology Taught by Viruses

  1996cited by this paper
• Interleukin (IL) 4, in the absence of antigen stimulation, induces an anergy-like state in differentiated CD8+ TC1 cells: loss of IL-2 synthesis and autonomous proliferation but retention of cytotoxicity and synthesis of other cytokines

  1995cited by this paper
• The roles of perforin‐ and Fas‐dependent cytotoxicity in protection against cytopathic and noncytopathic viruses

  1995cited by this paper
• Cytokine-induced differentiation of precursor mouse CD8+ T cells into cytotoxic CD8+ T cells secreting Th1 or Th2 cytokines.

  1995cited by this paper
• Protection against Fas-dependent Thl-mediated apoptosis by antigen receptor engagement in B cells

  1995cited by this paper
• Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity.

  1994cited by this paper
• Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice

  1994cited by this paper
• Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways

  1994cited by this paper
• CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection

  1994cited by this paper
• Generation of polarized antigen-specific CD8 effector populations: reciprocal action of interleukin (IL)-4 and IL-12 in promoting type 2 versus type 1 cytokine profiles

  1994cited by this paper
• Two distinct pathways of specific killing revealed by perforin mutant cytotoxic T lymphocytes.

  1994cited by this paper
• CD28-B7 interactions in T-cell activation.

  1994cited by this paper
• Immune function in mice lacking the perforin gene.

  1994cited by this paper
• Fas involvement in Ca(2+)-independent T cell-mediated cytotoxicity

  1993cited by this paper
• CD4+8− help prevents rapid deletion of CD8+ cells after a transient response to antigen

  1993cited by this paper
• CD8 T cells can protect against an intracellular bacterium in an interferon gamma-independent fashion.

  1992cited by this paper
• Regulation of lymphokine expression in T cell activation. I. Rapid loss of interleukin‐specific RNA after removal of the stimulating signal

  1991cited by this paper
• Effective clearance of mouse hepatitis virus from the central nervous system requires both CD4+ and CD8+ T cells

  1990cited by this paper
• Alloreactive murine CD8+ T cell clones secrete the Th1 pattern of cytokines.

  1990cited by this paper
• In vivo induction of antigen-specific transplantation tolerance to Qa1a by exposure to alloantigen in the absence of T-cell help.

  1990cited by this paper
• Cellular interactions in the humoral immune response.

  1989cited by this paper
• Specific assays for cytokine production by T cells.

  1989cited by this paper
• Antigen-specific activation of effector macrophages by IFN-gamma producing (TH1) T cell clones. Failure of IL-4-producing (TH2) T cell clones to activate effector function in macrophages.

  1989cited by this paper
• Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins.

  1986cited by this paper
• Serologic and functional characterization of a panel of antigen- presenting cell lines expressing mutant I-A class II molecules

  1983cited by this paper
• Autonomously proliferating K/D‐restricted cytolytic T cell clones

  1983cited by this paper
• Helper cell-independent cytotoxic clones in man

  1982cited by this paper
• Antigen-driven helper cell-independent cloned cytolytic T lymphocytes

  1981cited by this paper
• T-cell lines which cooperate in generation of specific cytolytic activity

  1979cited by this paper
• Fine specificity of a continuously growing killer cell clone specific for H‐Y antigen

  1979cited by this paper
• Cloned T-cell lines with specific cytolytic activity.

  1978cited by this paper
• T-T-cell interactions during the vitro cytotoxic allograft responses. I. Soluble products from activated Lyl+ T cells trigger autonomously antigen-primed Ly23+ T cells to cell proliferation and cytolytic activity

  1978cited by this paper
• Long term culture of tumour-specific cytotoxic T cells

  1977cited by this paper

• MAIT cells induced by engineered Listeria exhibit antibacterial and antitumor activity

  2025cites this paper
• Low Percentage of Perforin-Expressing NK Cells during Severe SARS-CoV-2 Infection: Consumption Rather than Primary Deficiency.

  2024cites this paper
• Low perforin expression in CD8+ T lymphocytes during the acute phase of severe SARS-CoV-2 infection predicts long COVID

  2022cites this paper
• Combined use of live-attenuated and inactivated influenza vaccines to enhance heterosubtypic protection.

  2018cites this paper
• IL-4-Deficient Mice Enhanced Cytotoxic T Cell Activity in

  2017cites this paper
• Culling of APCs by inflammatory cell death pathways restricts TIM3 and PD-1 expression and promotes the survival of primed CD8 T cells

  2017cites this paper
• Longitudinal multiparameter assay of lymphocyte interactions from onset by microfluidic cell pairing and culture

  2016cites this paper
• Intrinsic Contribution of Perforin to NK-Cell Homeostasis during Mouse Cytomegalovirus Infection

  2016cites this paper
• The specific NK cell response in concert with perforin prevents CD8+ T cell-mediated immunopathology after mouse cytomegalovirus infection

  2015cites this paper
• Large T Antigen-Specific Cytotoxic T Cells Protect Against Dendritic Cell Tumors through Perforin-Mediated Mechanisms Independent of CD4 T Cell Help

  2014cites this paper
• Adoptive Transfer of Tc1 or Tc17 Cells Elicits Antitumor Immunity against Established Melanoma through Distinct Mechanisms

  2013cites this paper
• -Mediated MHC Up-Regulation γ the Central Nervous System Requires IFN- Perforin-Mediated Effector Function Within

  2013cites this paper
• This information is current as Dendritic Cells In Vivo Lipopolysaccharide-Induced Apoptosis of Lymphocytes Regulate Cutting Edge: Antigen-Specific T

  2013cites this paper
• MechanismsEstablished Melanoma through Distinct Elicits Antitumor Immunity against Adoptive Transfer of Tc1 or Tc17 Cells

  2013cites this paper
• Participação das células T de memória e linfócitos CD4.CD25+Foxp3 (reguladores) nos mecanismos de resistência à infecção experimental pelo trypanosoma cruzi

  2013cites this paper
• Inefficient boosting of antitumor CD8+ T cells by dendritic-cell vaccines is rescued by restricting T-cell cytotoxic functions

  2012cites this paper
• Epitope specificity of memory CD8+ T cells dictates vaccination‐induced mortality in LCMV‐infected perforin‐deficient mice

  2012cites this paper
• A high-throughput single-cell analysis of human CD8⁺ T cell functions reveals discordance for cytokine secretion and cytolysis.

  2011cites this paper
• The Role of CD8+ T Cell Phenotype and Cytotoxicity on Cancer Immunotherapy

  2011cites this paper
• IFN-γ Expressed by T Cells Regulates the Persistence of Antigen Presentation by Limiting the Survival of Dendritic Cells1

  2009cites this paper
• The gut mucosa as a site for induction of regulatory T-cells.

  2009cites this paper
• Oral tolerance: can we make it work?

  2009cites this paper
• Limiting the Survival of Dendritic Cells Persistence of Antigen Presentation by Expressed by T Cells Regulates the g IFN-Subash

  2009cites this paper
• Dissociated Induction of Cytotoxicity and DTH by CFA and CpG

  2009cites this paper
• Immune Responses in Perforin Deficient Mice

  2009cites this paper
• Adjuvant guided T cell responses.

  2009cites this paper
• Role of the perforin/granzyme cell death pathway in D-Gal/LPS-induced inflammatory liver injury.

  2009cites this paper
• Killing by Cytotoxic T Lymphocytes In Vivo Protease Inhibitor 6 and Remain Sensitive to Lipopolysaccharide UpRegulate Serine Dendritic Cells Treated with Ritchie

  2008cites this paper
• Dendritic Cells Treated with Lipopolysaccharide Up-Regulate Serine Protease Inhibitor 6 and Remain Sensitive to Killing by Cytotoxic T Lymphocytes In Vivo1

  2008cites this paper
• Early diagnostic and prognostic significance of a specific Th1/Th2 cytokine pattern in children with haemophagocytic syndrome

  2008cites this paper
• Contribution of CD8+ T Cells to Control of Mycobacterium tuberculosis Infection1

  2006cites this paper
• This information is current as Infection Mycobacterium tuberculosis T Cells to Control of + Contribution of CD 8 Kirschner

  2006cites this paper
• Contribution of CD8+ T cells to control of Mycobacterium tuberculosis infection.

  2006cites this paper
• Perforin deficiency attenuates collagen-induced arthritis

  2005cites this paper
• Long-Term Control of Mycobacterium tuberculosis Infection Is Mediated by Dynamic Immune Responses

  2005cites this paper
• Combined CD4+ Th1 effect and lymphotactin transgene expression enhance CD8+ Tc1 tumor localization and therapy

  2005cites this paper
• Long-Term Control of Mycobacterium tuberculosis Infection Is Mediated by Dynamic Immune Responses1

  2005cites this paper
• Both perforin and Fas ligand are required for the regulation of alloreactive CD8+ T cells during acute graft-versus-host disease.

  2005cites this paper
• ANTIEGRESSIN ACTS LATE IN THE INTRACELLULAR GROWTH CYCLE OF TRYPANOSOMA CRUZI TO INHIBIT PARASITE EGRESS

  2004cites this paper
• Dependence on IL-4 Production T Cells and + Mediation by Type 2 CD8 Administration of B7-Ig Fusion Proteins: Induction of Tumor Regression by

  2004cites this paper
• Phenotypic and functional characteristics of CD28+ and CD28− cells from chagasic patients: distinct repertoire and cytokine expression

  2004cites this paper
• Induction of Tumor Regression by Administration of B7-Ig Fusion Proteins: Mediation by Type 2 CD8+ T Cells and Dependence on IL-4 Production1

  2004cites this paper
• PRIMING AND MAINTENANCE OF MYCOBACTERIUM TUBERCULOSIS SPECIFIC T CELL RESPONSES

  2004cites this paper
• Macrophages Directly Prime Naïve CD8+ T Cells: a Dissertation

  2004cites this paper
• Committed memory effector type 2 cytotoxic T (Tc2) cells are ineffective in protective anti-tumor immunity.

  2004cites this paper
• DISCOVERY AND CHARACTERIZATION OF AN ANTIBODY, ANTI-EGRESSIN, THAT IS ABLE TO INHIBIT TRYPANOSOMA CRUZI EGRESS IN VITRO

  2004cites this paper
• Profiling the CD8low phenotype, an alternative career choice for CD8 T cells during primary differentiation

  2004cites this paper
• HIV-1 transgenic rats develop T cell abnormalities.

  2004cites this paper
• Maintenance and attrition of T-cell memory.

  2003cites this paper
• Feedback regulation of pathogen-specific T cell priming.

  2003cites this paper
• Perforin and the granule exocytosis cytotoxicity pathway.

  2003cites this paper
• Antigen-independent cross-talk between macrophages and CD8+ T cells facilitates their cooperation during target destruction.

  2003cites this paper
• Perforin-Mediated Effector Function Within the Central Nervous System Requires IFN-γ-Mediated MHC Up-Regulation1

  2003cites this paper
• The Frequency of Type 2 CD8+ T Cells Is Increased in Peripheral Blood from Patients with Psoriasis Vulgaris

  2003cites this paper
• Archaeosomes induce enhanced cytotoxic T lymphocyte responses to entrapped soluble protein in the absence of interleukin 12 and protect against tumor challenge.

  2003cites this paper
• T cell memory.

  2003cites this paper
• Mouse Vascular Endothelium Activates CD8+ T Lymphocytes in a B7-Dependent Fashion1

  2002cites this paper
• Multiple Mechanisms Compensate to Enhance Tumor-Protective CD8+ T Cell Response in the Long-Term Despite Poor CD8+ T Cell Priming Initially: Comparison Between an Acute Versus a Chronic Intracellular Bacterium Expressing a Model Antigen1

  2002cites this paper
• Suppression of Lymphoma and Epithelial Malignancies Effected by Interferon γ

  2002cites this paper
• T CELLS AND THE PRIMARY IMMUNE RESPONSE

  2002cites this paper
• Antigen Intracellular Bacterium Expressing a Model Between an Acute Versus a Chronic T Cell Priming Initially : Comparison + CD 8 Response in the Long-Term Despite Poor T Cell + Enhance Tumor-Protective CD 8 Multiple Mechanisms Compensate to

  2002cites this paper
• Role of Effector Cell-Derived IL-4, IL-5, and Perforin in Early and Late Stages of Type 2 CD8 Effector Cell-Mediated Tumor Rejection1

  2001cites this paper
• Detection and analysis of antigen-specific CD8+ T cells

  2001cites this paper
• The effect of IFNγ on the hepatocyte: cell cycle and apoptosis

  2001cites this paper
• Counter-regulation of cytolytic activity and cytokine production in HIV-1-specific murine CD8+ cytotoxic T lymphocytes by free antigenic peptide.

  2001cites this paper
• CD8 Effector Cell-Mediated Tumor Rejection Perforin in Early and Late Stages of Type 2 Role of Effector Cell-Derived IL-4, IL-5, and

  2001cites this paper
• The effect of IFNgamma on the hepatocyte: cell cycle and apoptosis.

  2001cites this paper
• Immunopotentiating role of IFN-gamma in early and late stages of type 1 CD8 effector cell-mediated tumor rejection.

  2001cites this paper
• Modulation of CD8+ T Cell Response to Antigen by the Levels of Self MHC Class I1

  2001cites this paper
• Perforin‐independent regulation of dendritic cell homeostasis by CD8+ T cells in vivo: implications for adaptive immunotherapy

  2001cites this paper
• Hsp70 in immunotherapy : a potential vector in cancer and viral vaccines

  2000cites this paper
• Trypanosoma cruzi: roles for perforin-dependent and perforin-independent immune mechanisms in acute resistance.

  2000cites this paper
• Cutting Edge: Antilisterial Activity of CD8+ T Cells Derived from TNF-Deficient and TNF/Perforin Double-Deficient Mice1

  2000cites this paper
• TNF / Perforin Double-Deficient Mice T Cells Derived from TNF-Deficient and + Cutting Edge : Antilisterial Activity of CD 8 and

  2000cites this paper
• Cells Is Antigen Independent T + Production by Antigen-Specific CD8 Cutting Edge: OFF Cycling of TNF

  2000cites this paper
• Archaeosomes Induce Long-Term CD8+ Cytotoxic T Cell Response to Entrapped Soluble Protein by the Exogenous Cytosolic Pathway, in the Absence of CD4+ T Cell Help1

  2000cites this paper
• Cutting Edge: OFF Cycling of TNF Production by Antigen-Specific CD8+ T Cells Is Antigen Independent1

  2000cites this paper
• T Cell + Pathway, in the Absence of CD4 Soluble Protein by the Exogenous Cytosolic Cytotoxic T Cell Response to Entrapped + Archaeosomes Induce Long-Term CD8

  2000cites this paper
• Regulation of antigen-specific CD8+ T cell homeostasis by perforin and interferon-gamma.

  2000cites this paper
• Role of CD8+ T cells in mycobacterial infections

  2000cites this paper
• A Role for Perforin in Downregulating T-Cell Responses during Chronic Viral Infection

  1999cites this paper
• Perforin-deficient CD8+ T cells: in vivo priming and antigen-specific immunity against Listeria monocytogenes.

  1999cites this paper
• Characterization of Human Mycobacterium bovis Bacille Calmette-Guérin-Reactive CD8+T Cells

  1999cites this paper
• Therapeutic effects of tumor-reactive type 1 and type 2 CD8+ T cell subpopulations in established pulmonary metastases.

  1999cites this paper
• The Virus-Specific CD4+ T Cell Response During Acute Lymphocytic Choriomeningitis Virus Infection and into Long Term Memory: a Dissertation

  1999cites this paper
• Enhanced cytotoxic T cell activity in IL-4-deficient mice.

  1999cites this paper
• Shaping the repertoire of cytotoxic T-lymphocyte responses: explanation for the immunodominance effect whereby cytotoxic T lymphocytes specific for immunodominant antigens prevent recognition of nondominant antigens.

  1999cites this paper
• Established Pulmonary Metastases T Cell Subpopulations in + 1 and Type 2 CD8 Therapeutic Effects of Tumor-Reactive Type

  1999cites this paper
• The in vivo fate of APCs displaying minor H antigen and/or MHC differences is regulated by CTLs specific for immunodominant class I-associated epitopes.

  1999cites this paper
• Homeostatic regulation of CD8+ T cells by perforin

  1999cites this paper
• Cytokine deprivation of naive CD8+ T cells promotes minimal cell cycling but maximal cytokine synthesis and autonomous proliferation subsequently: a mechanism of self-regulation.

  1999cites this paper
• Epitopes Immunodominant Class I-Associated Regulated by CTLs Specific for H Antigen and / or MHC Differences Is The In Vivo Fate of APCs Displaying Minor

  1999cites this paper
• Death A Role for Perforin in Activation-Induced Cell

  1998cites this paper
• A role for perforin in activation-induced cell death.

  1998cites this paper
• Induction and Exhaustion of Lymphocytic Choriomeningitis Virus–specific Cytotoxic T Lymphocytes Visualized Using Soluble Tetrameric Major Histocompatibility Complex Class I–Peptide Complexes

  1998cites this paper
• Antigen-specific T lymphocytes regulate lipopolysaccharide-induced apoptosis of dendritic cells in vivo.

  1998cites this paper
• Stability of virus-specific CD4+ T cell frequencies from acute infection into long term memory.

  1998cites this paper
• In vivo persistence of CD8 polarized T cell subsets producing type 1 or type 2 cytokines.

  1998cites this paper
• Term Frequencies from Acute Infection into Long T Cell + Stability of Virus-Specific CD4

  1998cites this paper
• Enhanced antibody and cytokine responses to influenza viral antigens in perforin-deficient mice.

  1998cites this paper