Abstract
Recent studies have implicated the cell surface receptor Programmed Death-1 (PD-1) in numerous models of T cell anergy, though the specific mechanisms by which the PD-1 signal maintains tolerance is not clear. We demonstrate that the depletion of PD-1 with siRNA results in a complete reversal of clonal anergy in the A.E7 T cell model, suggesting that the mechanism by which PD-1 maintains the anergic phenotype is a T-cell-intrinsic phenomenon, and not one dependent on other cell populations in vivo. We have also shown that the neutralization of IL-2 during restimulation abrogates the effect of PD-1 depletion, suggesting that tolerance mediated by PD-1 is wholly IL-2 dependent, and likewise intrinsic to the tolerized cells.
MeSH terms
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Animals
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Antigens / administration & dosage
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Antigens, Surface / genetics
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Antigens, Surface / metabolism
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Apoptosis Regulatory Proteins / antagonists & inhibitors*
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism
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Base Sequence
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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Cell Line
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Cell Proliferation
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Clonal Anergy / genetics
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Clonal Anergy / immunology*
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Columbidae
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Cytochromes c / immunology
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DNA Primers / genetics
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Interleukin-2 / antagonists & inhibitors
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Interleukin-2 / metabolism
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Mice
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Mice, Inbred BALB C
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Phenotype
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Programmed Cell Death 1 Receptor
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Small Interfering / genetics
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Signal Transduction / immunology
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Transfection
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Transplantation Tolerance / genetics
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Transplantation Tolerance / immunology
Substances
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Antigens
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Antigens, Surface
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Apoptosis Regulatory Proteins
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DNA Primers
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Interleukin-2
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Pdcd1 protein, mouse
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Programmed Cell Death 1 Receptor
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RNA, Messenger
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RNA, Small Interfering
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Cytochromes c