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Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR–induced stop signal
by
Obu, Takashi
, Pauken, Kristen E
, Wu, Jenny
, Eagar, Todd N
, Tang, Qizhi
, Bluestone, Jeffrey A
, Azuma, Miyuki
, Krummel, Matthew F
, Fife, Brian T
in
Animals
/ Antigens, CD - immunology
/ Antigens, CD - metabolism
/ Antigens, Surface - immunology
/ Antigens, Surface - metabolism
/ Apoptosis Regulatory Proteins - immunology
/ Apoptosis Regulatory Proteins - metabolism
/ B7-1 Antigen - immunology
/ B7-1 Antigen - metabolism
/ B7-H1 Antigen
/ Biomedical and Life Sciences
/ Biomedicine
/ Cell Movement
/ Cell receptors
/ Cellular signal transduction
/ CTLA-4 Antigen
/ Dendritic Cells - immunology
/ Diabetes Mellitus, Experimental - immunology
/ Diabetes Mellitus, Experimental - metabolism
/ Diabetes Mellitus, Type 1 - immunology
/ Diabetes Mellitus, Type 1 - metabolism
/ Immune Tolerance
/ Immunology
/ Infectious Diseases
/ Islets of Langerhans - immunology
/ Islets of Langerhans - metabolism
/ Islets of Langerhans Transplantation
/ Lymph nodes
/ Lymphocyte Activation
/ Membrane Glycoproteins - immunology
/ Membrane Glycoproteins - metabolism
/ Mice
/ Mice, Inbred C57BL
/ Mice, Inbred NOD
/ Mice, Transgenic
/ Peptides - immunology
/ Peptides - metabolism
/ Physiological aspects
/ Programmed Cell Death 1 Receptor
/ Receptors, Antigen, T-Cell - immunology
/ Signal Transduction - immunology
/ T cells
2009
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Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR–induced stop signal
by
Obu, Takashi
, Pauken, Kristen E
, Wu, Jenny
, Eagar, Todd N
, Tang, Qizhi
, Bluestone, Jeffrey A
, Azuma, Miyuki
, Krummel, Matthew F
, Fife, Brian T
in
Animals
/ Antigens, CD - immunology
/ Antigens, CD - metabolism
/ Antigens, Surface - immunology
/ Antigens, Surface - metabolism
/ Apoptosis Regulatory Proteins - immunology
/ Apoptosis Regulatory Proteins - metabolism
/ B7-1 Antigen - immunology
/ B7-1 Antigen - metabolism
/ B7-H1 Antigen
/ Biomedical and Life Sciences
/ Biomedicine
/ Cell Movement
/ Cell receptors
/ Cellular signal transduction
/ CTLA-4 Antigen
/ Dendritic Cells - immunology
/ Diabetes Mellitus, Experimental - immunology
/ Diabetes Mellitus, Experimental - metabolism
/ Diabetes Mellitus, Type 1 - immunology
/ Diabetes Mellitus, Type 1 - metabolism
/ Immune Tolerance
/ Immunology
/ Infectious Diseases
/ Islets of Langerhans - immunology
/ Islets of Langerhans - metabolism
/ Islets of Langerhans Transplantation
/ Lymph nodes
/ Lymphocyte Activation
/ Membrane Glycoproteins - immunology
/ Membrane Glycoproteins - metabolism
/ Mice
/ Mice, Inbred C57BL
/ Mice, Inbred NOD
/ Mice, Transgenic
/ Peptides - immunology
/ Peptides - metabolism
/ Physiological aspects
/ Programmed Cell Death 1 Receptor
/ Receptors, Antigen, T-Cell - immunology
/ Signal Transduction - immunology
/ T cells
2009
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Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR–induced stop signal
by
Obu, Takashi
, Pauken, Kristen E
, Wu, Jenny
, Eagar, Todd N
, Tang, Qizhi
, Bluestone, Jeffrey A
, Azuma, Miyuki
, Krummel, Matthew F
, Fife, Brian T
in
Animals
/ Antigens, CD - immunology
/ Antigens, CD - metabolism
/ Antigens, Surface - immunology
/ Antigens, Surface - metabolism
/ Apoptosis Regulatory Proteins - immunology
/ Apoptosis Regulatory Proteins - metabolism
/ B7-1 Antigen - immunology
/ B7-1 Antigen - metabolism
/ B7-H1 Antigen
/ Biomedical and Life Sciences
/ Biomedicine
/ Cell Movement
/ Cell receptors
/ Cellular signal transduction
/ CTLA-4 Antigen
/ Dendritic Cells - immunology
/ Diabetes Mellitus, Experimental - immunology
/ Diabetes Mellitus, Experimental - metabolism
/ Diabetes Mellitus, Type 1 - immunology
/ Diabetes Mellitus, Type 1 - metabolism
/ Immune Tolerance
/ Immunology
/ Infectious Diseases
/ Islets of Langerhans - immunology
/ Islets of Langerhans - metabolism
/ Islets of Langerhans Transplantation
/ Lymph nodes
/ Lymphocyte Activation
/ Membrane Glycoproteins - immunology
/ Membrane Glycoproteins - metabolism
/ Mice
/ Mice, Inbred C57BL
/ Mice, Inbred NOD
/ Mice, Transgenic
/ Peptides - immunology
/ Peptides - metabolism
/ Physiological aspects
/ Programmed Cell Death 1 Receptor
/ Receptors, Antigen, T-Cell - immunology
/ Signal Transduction - immunology
/ T cells
2009
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Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR–induced stop signal
Journal Article
Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR–induced stop signal
2009
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Overview
The inhibitory protein PD-1 is expressed on activated T cells. Fife and colleagues find that interactions between PD-1 and its ligand PD-1L are needed to maintain tolerance and prevent interactions between tolerized T cells and dendritic cells.
Programmed death 1 (PD-1) is an inhibitory molecule expressed on activated T cells; however, the biological context in which PD-1 controls T cell tolerance remains unclear. Using two-photon laser-scanning microscopy, we show here that unlike naive or activated islet antigen–specific T cells, tolerized islet antigen–specific T cells moved freely and did not swarm around antigen-bearing dendritic cells (DCs) in pancreatic lymph nodes. Inhibition of T cell antigen receptor (TCR)-driven stop signals depended on continued interactions between PD-1 and its ligand, PD-L1, as antibody blockade of PD-1 or PD-L1 resulted in lower T cell motility, enhanced T cell–DC contacts and caused autoimmune diabetes. Blockade of the immunomodulatory receptor CTLA-4 did not alter T cell motility or abrogate tolerance. Thus, PD-1–PD-L1 interactions maintain peripheral tolerance by mechanisms fundamentally distinct from those of CTLA-4.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Antigens, Surface - immunology
/ Antigens, Surface - metabolism
/ Apoptosis Regulatory Proteins - immunology
/ Apoptosis Regulatory Proteins - metabolism
/ Biomedical and Life Sciences
/ Cellular signal transduction
/ Dendritic Cells - immunology
/ Diabetes Mellitus, Experimental - immunology
/ Diabetes Mellitus, Experimental - metabolism
/ Diabetes Mellitus, Type 1 - immunology
/ Diabetes Mellitus, Type 1 - metabolism
/ Islets of Langerhans - immunology
/ Islets of Langerhans - metabolism
/ Islets of Langerhans Transplantation
/ Membrane Glycoproteins - immunology
/ Membrane Glycoproteins - metabolism
/ Mice
/ Programmed Cell Death 1 Receptor
/ Receptors, Antigen, T-Cell - immunology
/ Signal Transduction - immunology
/ T cells
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