Programmed death (PD)-1:PD-ligand 1/PD-ligand 2 pathway inhibits T cell effector functions during human tuberculosis
Protective immunity against Mycobacterium tuberculosis requires the generation of cell-mediated immunity. We investigated the expression and role of programmed death 1 (PD-1) and its ligands, molecules known to modulate T cell activation, in the regulation of IFN-γ production and lytic degranulation...
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2008
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v181_n1_p116_Jurado http://hdl.handle.net/20.500.12110/paper_00221767_v181_n1_p116_Jurado |
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paper:paper_00221767_v181_n1_p116_Jurado2023-06-08T14:46:56Z Programmed death (PD)-1:PD-ligand 1/PD-ligand 2 pathway inhibits T cell effector functions during human tuberculosis gamma interferon inhibitor protein ligand pd 1 ligand pd 2 ligand programmed death 1 protein receptor protein unclassified drug antigen apoptosis regulatory protein CD150 antigen CD274 protein, human cell surface receptor gamma interferon leukocyte antigen PDCD1 protein, human PDCD1LG2 protein, human signal peptide article CD3+ T lymphocyte CD8+ T lymphocyte cellular immunity cytokine production degranulation human priority journal protein expression protein function signal transduction T lymphocyte activation tuberculosis biosynthesis cell culture immunology lymphocyte activation metabolism Mycobacterium tuberculosis protein binding signal transduction T lymphocyte Antigens Antigens, CD Apoptosis Regulatory Proteins Cells, Cultured Humans Intercellular Signaling Peptides and Proteins Interferon Type II Lymphocyte Activation Mycobacterium tuberculosis Protein Binding Receptors, Cell Surface Signal Transduction T-Lymphocytes Tuberculosis Protective immunity against Mycobacterium tuberculosis requires the generation of cell-mediated immunity. We investigated the expression and role of programmed death 1 (PD-1) and its ligands, molecules known to modulate T cell activation, in the regulation of IFN-γ production and lytic degranulation during human tuberculosis. We demonstrated that specific Ag-stimulation increased CD3+PD-1+ lymphocytes in peripheral blood and pleural fluid from tuberculosis patients in direct correlation with IFN-γ production from these individuals. Moreover, M. tuberculosis-induced IFN-γ participated in the up-regulation of PD-1 expression. Blockage of PD-1 or PD-1 and its ligands (PD-Ls: PD-L1, PD-L2) enhanced the specific degranulation of CD8+ T cells and the percentage, of specific IFN-γ-producing lymphocytes against the pathogen, demonstrating that the PD-1:PD-Ls pathway inhibits T cell effector functions during active M. tuberculosis infection. Furthermore, the simultaneous blockage of the inhibitory receptor PD-1 together with the activation of the costimulatory protein signaling lymphocytic activation molecule led to the promotion of protective IFN-γ responses to M. tuberculosis, even in patients with weak cell-mediated immunity against the bacteria. Together, we demonstrated that PD-1 interferes with T cell effector functions against M. tuberculosis, suggesting that PD-1 has a key regulatory role during the immune response of the host to the pathogen. Copyright © 2008 by The American Association of Immunologists, Inc. 2008 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v181_n1_p116_Jurado http://hdl.handle.net/20.500.12110/paper_00221767_v181_n1_p116_Jurado |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
gamma interferon inhibitor protein ligand pd 1 ligand pd 2 ligand programmed death 1 protein receptor protein unclassified drug antigen apoptosis regulatory protein CD150 antigen CD274 protein, human cell surface receptor gamma interferon leukocyte antigen PDCD1 protein, human PDCD1LG2 protein, human signal peptide article CD3+ T lymphocyte CD8+ T lymphocyte cellular immunity cytokine production degranulation human priority journal protein expression protein function signal transduction T lymphocyte activation tuberculosis biosynthesis cell culture immunology lymphocyte activation metabolism Mycobacterium tuberculosis protein binding signal transduction T lymphocyte Antigens Antigens, CD Apoptosis Regulatory Proteins Cells, Cultured Humans Intercellular Signaling Peptides and Proteins Interferon Type II Lymphocyte Activation Mycobacterium tuberculosis Protein Binding Receptors, Cell Surface Signal Transduction T-Lymphocytes Tuberculosis |
| spellingShingle |
gamma interferon inhibitor protein ligand pd 1 ligand pd 2 ligand programmed death 1 protein receptor protein unclassified drug antigen apoptosis regulatory protein CD150 antigen CD274 protein, human cell surface receptor gamma interferon leukocyte antigen PDCD1 protein, human PDCD1LG2 protein, human signal peptide article CD3+ T lymphocyte CD8+ T lymphocyte cellular immunity cytokine production degranulation human priority journal protein expression protein function signal transduction T lymphocyte activation tuberculosis biosynthesis cell culture immunology lymphocyte activation metabolism Mycobacterium tuberculosis protein binding signal transduction T lymphocyte Antigens Antigens, CD Apoptosis Regulatory Proteins Cells, Cultured Humans Intercellular Signaling Peptides and Proteins Interferon Type II Lymphocyte Activation Mycobacterium tuberculosis Protein Binding Receptors, Cell Surface Signal Transduction T-Lymphocytes Tuberculosis Programmed death (PD)-1:PD-ligand 1/PD-ligand 2 pathway inhibits T cell effector functions during human tuberculosis |
| topic_facet |
gamma interferon inhibitor protein ligand pd 1 ligand pd 2 ligand programmed death 1 protein receptor protein unclassified drug antigen apoptosis regulatory protein CD150 antigen CD274 protein, human cell surface receptor gamma interferon leukocyte antigen PDCD1 protein, human PDCD1LG2 protein, human signal peptide article CD3+ T lymphocyte CD8+ T lymphocyte cellular immunity cytokine production degranulation human priority journal protein expression protein function signal transduction T lymphocyte activation tuberculosis biosynthesis cell culture immunology lymphocyte activation metabolism Mycobacterium tuberculosis protein binding signal transduction T lymphocyte Antigens Antigens, CD Apoptosis Regulatory Proteins Cells, Cultured Humans Intercellular Signaling Peptides and Proteins Interferon Type II Lymphocyte Activation Mycobacterium tuberculosis Protein Binding Receptors, Cell Surface Signal Transduction T-Lymphocytes Tuberculosis |
| description |
Protective immunity against Mycobacterium tuberculosis requires the generation of cell-mediated immunity. We investigated the expression and role of programmed death 1 (PD-1) and its ligands, molecules known to modulate T cell activation, in the regulation of IFN-γ production and lytic degranulation during human tuberculosis. We demonstrated that specific Ag-stimulation increased CD3+PD-1+ lymphocytes in peripheral blood and pleural fluid from tuberculosis patients in direct correlation with IFN-γ production from these individuals. Moreover, M. tuberculosis-induced IFN-γ participated in the up-regulation of PD-1 expression. Blockage of PD-1 or PD-1 and its ligands (PD-Ls: PD-L1, PD-L2) enhanced the specific degranulation of CD8+ T cells and the percentage, of specific IFN-γ-producing lymphocytes against the pathogen, demonstrating that the PD-1:PD-Ls pathway inhibits T cell effector functions during active M. tuberculosis infection. Furthermore, the simultaneous blockage of the inhibitory receptor PD-1 together with the activation of the costimulatory protein signaling lymphocytic activation molecule led to the promotion of protective IFN-γ responses to M. tuberculosis, even in patients with weak cell-mediated immunity against the bacteria. Together, we demonstrated that PD-1 interferes with T cell effector functions against M. tuberculosis, suggesting that PD-1 has a key regulatory role during the immune response of the host to the pathogen. Copyright © 2008 by The American Association of Immunologists, Inc. |
| title |
Programmed death (PD)-1:PD-ligand 1/PD-ligand 2 pathway inhibits T cell effector functions during human tuberculosis |
| title_short |
Programmed death (PD)-1:PD-ligand 1/PD-ligand 2 pathway inhibits T cell effector functions during human tuberculosis |
| title_full |
Programmed death (PD)-1:PD-ligand 1/PD-ligand 2 pathway inhibits T cell effector functions during human tuberculosis |
| title_fullStr |
Programmed death (PD)-1:PD-ligand 1/PD-ligand 2 pathway inhibits T cell effector functions during human tuberculosis |
| title_full_unstemmed |
Programmed death (PD)-1:PD-ligand 1/PD-ligand 2 pathway inhibits T cell effector functions during human tuberculosis |
| title_sort |
programmed death (pd)-1:pd-ligand 1/pd-ligand 2 pathway inhibits t cell effector functions during human tuberculosis |
| publishDate |
2008 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00221767_v181_n1_p116_Jurado http://hdl.handle.net/20.500.12110/paper_00221767_v181_n1_p116_Jurado |
| _version_ |
1768544396038373376 |