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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2008-6-20
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pubmed:abstractText |
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-gamma 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-gamma production from these individuals. Moreover, M. tuberculosis-induced IFN-gamma 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-gamma-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-gamma 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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD274,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/CD150 antigen,
http://linkedlifedata.com/resource/pubmed/chemical/CD274 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/PDCD1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PDCD1LG2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Programmed Cell Death 1 Ligand 2...,
http://linkedlifedata.com/resource/pubmed/chemical/Programmed Cell Death 1 Receptor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
181
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
116-25
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:18566376-Antigens,
pubmed-meshheading:18566376-Antigens, CD,
pubmed-meshheading:18566376-Antigens, CD274,
pubmed-meshheading:18566376-Apoptosis Regulatory Proteins,
pubmed-meshheading:18566376-Cells, Cultured,
pubmed-meshheading:18566376-Humans,
pubmed-meshheading:18566376-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:18566376-Interferon-gamma,
pubmed-meshheading:18566376-Lymphocyte Activation,
pubmed-meshheading:18566376-Mycobacterium tuberculosis,
pubmed-meshheading:18566376-Programmed Cell Death 1 Ligand 2 Protein,
pubmed-meshheading:18566376-Programmed Cell Death 1 Receptor,
pubmed-meshheading:18566376-Protein Binding,
pubmed-meshheading:18566376-Receptors, Cell Surface,
pubmed-meshheading:18566376-Signal Transduction,
pubmed-meshheading:18566376-T-Lymphocytes,
pubmed-meshheading:18566376-Tuberculosis
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pubmed:year |
2008
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pubmed:articleTitle |
Programmed death (PD)-1:PD-ligand 1/PD-ligand 2 pathway inhibits T cell effector functions during human tuberculosis.
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pubmed:affiliation |
Department of Biological Chemistry, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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