Role of PD-1 and its ligand, B7-H1, in early fate decisions of CD8 T cells
Expression of the PD-1 receptor on T cells has been shown to provide an important inhibitory signal that down-modulates peripheral effector responses in normal tissues and tumors. Furthermore, PD-1 up-regulation on chronically activated T cells can maintain them in a partially reversible inactive state. The function of PD-1 in the very early stages of T-cell response to antigen in vivo has not been fully explored. In this study, we evaluate the role of PD-1 and its 2 B7 family ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), in early fate decisions of CD8 T cells. We show that CD8 T cells specific for influenza hemagglutinin (HA) expressed as a self-antigen become functionally tolerized and express high levels of surface PD-1 by the time of their first cell division. Blockade of PD-1 or B7-H1, but not B7-DC, at the time of self-antigen encounter mitigates tolerance induction and results in CD8 T-cell differentiation into functional cytolytic T lymphocytes (CTLs). These findings demonstrate that, in addition to modulating effector functions in the periphery, B7-H1:PD-1 interactions regulate early T-cell-fate decisions.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2007 |
|---|---|
| Erschienen: |
2007 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:110 |
|---|---|
| Enthalten in: |
Blood - 110(2007), 1 vom: 01. Juli, Seite 186-92 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Goldberg, Monica V [VerfasserIn] |
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| Anmerkungen: |
Date Completed 27.09.2007 Date Revised 06.02.2021 published: Print-Electronic Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM169281558 |
|---|
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| 100 | 1 | |a Goldberg, Monica V |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Role of PD-1 and its ligand, B7-H1, in early fate decisions of CD8 T cells |
| 264 | 1 | |c 2007 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Revised 06.02.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Expression of the PD-1 receptor on T cells has been shown to provide an important inhibitory signal that down-modulates peripheral effector responses in normal tissues and tumors. Furthermore, PD-1 up-regulation on chronically activated T cells can maintain them in a partially reversible inactive state. The function of PD-1 in the very early stages of T-cell response to antigen in vivo has not been fully explored. In this study, we evaluate the role of PD-1 and its 2 B7 family ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), in early fate decisions of CD8 T cells. We show that CD8 T cells specific for influenza hemagglutinin (HA) expressed as a self-antigen become functionally tolerized and express high levels of surface PD-1 by the time of their first cell division. Blockade of PD-1 or B7-H1, but not B7-DC, at the time of self-antigen encounter mitigates tolerance induction and results in CD8 T-cell differentiation into functional cytolytic T lymphocytes (CTLs). These findings demonstrate that, in addition to modulating effector functions in the periphery, B7-H1:PD-1 interactions regulate early T-cell-fate decisions | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antigens, Surface |2 NLM | |
| 650 | 7 | |a Apoptosis Regulatory Proteins |2 NLM | |
| 650 | 7 | |a Autoantigens |2 NLM | |
| 650 | 7 | |a B7-1 Antigen |2 NLM | |
| 650 | 7 | |a B7-H1 Antigen |2 NLM | |
| 650 | 7 | |a Cd274 protein, mouse |2 NLM | |
| 650 | 7 | |a Membrane Glycoproteins |2 NLM | |
| 650 | 7 | |a Pdcd1 protein, mouse |2 NLM | |
| 650 | 7 | |a Pdcd1lg2 protein, mouse |2 NLM | |
| 650 | 7 | |a Peptides |2 NLM | |
| 650 | 7 | |a Programmed Cell Death 1 Ligand 2 Protein |2 NLM | |
| 650 | 7 | |a Programmed Cell Death 1 Receptor |2 NLM | |
| 700 | 1 | |a Maris, Charles H |e verfasserin |4 aut | |
| 700 | 1 | |a Hipkiss, Edward L |e verfasserin |4 aut | |
| 700 | 1 | |a Flies, Andrew S |e verfasserin |4 aut | |
| 700 | 1 | |a Zhen, Lijie |e verfasserin |4 aut | |
| 700 | 1 | |a Tuder, Rubin M |e verfasserin |4 aut | |
| 700 | 1 | |a Grosso, Joseph F |e verfasserin |4 aut | |
| 700 | 1 | |a Harris, Timothy J |e verfasserin |4 aut | |
| 700 | 1 | |a Getnet, Derese |e verfasserin |4 aut | |
| 700 | 1 | |a Whartenby, Katharine A |e verfasserin |4 aut | |
| 700 | 1 | |a Brockstedt, Dirk G |e verfasserin |4 aut | |
| 700 | 1 | |a Dubensky, Thomas W |c Jr |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Lieping |e verfasserin |4 aut | |
| 700 | 1 | |a Pardoll, Drew M |e verfasserin |4 aut | |
| 700 | 1 | |a Drake, Charles G |e verfasserin |4 aut | |
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