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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2011-2-17
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pubmed:abstractText |
Programmed cell death-1 (PD-1) is an inhibitory coreceptor for T lymphocytes that provides feedback inhibition of T cell activation. Although PD-1's expression on T cells is known to be activation dependent, the factors that determine the timing, intensity, and duration of PD-1 expression in immune reactions are not fully understood. To address this question, we performed a fine mapping analysis of a conserved 5'-flanking region of the PD-1 gene and identified a putative IFN stimulation response element, which was responsible for PD-1 transcription in the 2B4.11 T cell line. Consistent with this finding, activation by IFN-? enhanced both the induction and maintenance of PD-1 expression on TCR-engaged primary mouse T cells through an association IFN-responsive factor 9 (IRF9) to the IFN stimulation response element. Furthermore, PD-1 expression on Ag-specific CD8(+) T cells was augmented by IFN-? in vivo. We propose that strong innate inflammatory responses promote primary T cell activation and their differentiation into effector cells, but also cause an attenuated T cell response in sustained immune reactions, at least partially through type I IFN-mediated PD-1 transcription. Based on this idea, we demonstrate that IFN-? administration in combination with PD-1 blockade in tumor-bearing mice effectively augments the antitumor immunity, and we propose this as a novel and rational approach for cancer immunotherapy.
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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, Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-Stimulated Gene Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Isgf3g protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Pdcd1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Programmed Cell Death 1 Receptor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1550-6606
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
186
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2772-9
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:21263073-Animals,
pubmed-meshheading:21263073-Antigens, Surface,
pubmed-meshheading:21263073-Apoptosis Regulatory Proteins,
pubmed-meshheading:21263073-Cell Line,
pubmed-meshheading:21263073-Cell Line, Tumor,
pubmed-meshheading:21263073-Cells, Cultured,
pubmed-meshheading:21263073-Humans,
pubmed-meshheading:21263073-Immunity, Cellular,
pubmed-meshheading:21263073-Interferon-Stimulated Gene Factor 3, gamma Subunit,
pubmed-meshheading:21263073-Interferon-alpha,
pubmed-meshheading:21263073-Mice,
pubmed-meshheading:21263073-Mice, Inbred BALB C,
pubmed-meshheading:21263073-Mice, Inbred C57BL,
pubmed-meshheading:21263073-Mice, Knockout,
pubmed-meshheading:21263073-Mice, Transgenic,
pubmed-meshheading:21263073-Programmed Cell Death 1 Receptor,
pubmed-meshheading:21263073-Receptors, Antigen, T-Cell,
pubmed-meshheading:21263073-Regulatory Elements, Transcriptional,
pubmed-meshheading:21263073-Signal Transduction,
pubmed-meshheading:21263073-T-Lymphocyte Subsets,
pubmed-meshheading:21263073-Transcription, Genetic
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pubmed:year |
2011
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pubmed:articleTitle |
IFN-? directly promotes programmed cell death-1 transcription and limits the duration of T cell-mediated immunity.
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pubmed:affiliation |
Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida-konoe, Sakyo-Ku, Kyoto 606-8501, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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