Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal.

Research output: Contribution to journalArticle

Brian T. Fife, Kristen E. Pauken, Todd N. Eagar, Takashi Obu, Jenny Wu, Qizhi Tang, Miyuki Azuma, Matthew F. Krummel, Jeffrey A. Bluestone

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.

Original languageEnglish (US)
Pages (from-to)1185-1192
Number of pages8
JournalNature immunology
Volume10
Issue number11
DOIs
StatePublished - Jan 1 2009

PMID: 19783989

PMCID: PMC2778301

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Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. / Fife, Brian T.; Pauken, Kristen E.; Eagar, Todd N.; Obu, Takashi; Wu, Jenny; Tang, Qizhi; Azuma, Miyuki; Krummel, Matthew F.; Bluestone, Jeffrey A.

In: Nature immunology, Vol. 10, No. 11, 01.01.2009, p. 1185-1192.

Research output: Contribution to journalArticle

Harvard

Fife, BT, Pauken, KE, Eagar, TN, Obu, T, Wu, J, Tang, Q, Azuma, M, Krummel, MF & Bluestone, JA 2009, 'Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal.' Nature immunology, vol. 10, no. 11, pp. 1185-1192. https://doi.org/10.1038/ni.1790

APA

Fife, B. T., Pauken, K. E., Eagar, T. N., Obu, T., Wu, J., Tang, Q., ... Bluestone, J. A. (2009). Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. Nature immunology, 10(11), 1185-1192. https://doi.org/10.1038/ni.1790

Vancouver

Fife BT, Pauken KE, Eagar TN, Obu T, Wu J, Tang Q et al. Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. Nature immunology. 2009 Jan 1;10(11):1185-1192. https://doi.org/10.1038/ni.1790

Author

Fife, Brian T. ; Pauken, Kristen E. ; Eagar, Todd N. ; Obu, Takashi ; Wu, Jenny ; Tang, Qizhi ; Azuma, Miyuki ; Krummel, Matthew F. ; Bluestone, Jeffrey A. / Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. In: Nature immunology. 2009 ; Vol. 10, No. 11. pp. 1185-1192.

BibTeX

@article{925d9b6968b143e09a80c29c4f8e593b,
title = "Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal.",
abstract = "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.",
author = "Fife, {Brian T.} and Pauken, {Kristen E.} and Eagar, {Todd N.} and Takashi Obu and Jenny Wu and Qizhi Tang and Miyuki Azuma and Krummel, {Matthew F.} and Bluestone, {Jeffrey A.}",
year = "2009",
month = "1",
day = "1",
doi = "10.1038/ni.1790",
language = "English (US)",
volume = "10",
pages = "1185--1192",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "11",

}

RIS

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T1 - Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal.

AU - Fife, Brian T.

AU - Pauken, Kristen E.

AU - Eagar, Todd N.

AU - Obu, Takashi

AU - Wu, Jenny

AU - Tang, Qizhi

AU - Azuma, Miyuki

AU - Krummel, Matthew F.

AU - Bluestone, Jeffrey A.

PY - 2009/1/1

Y1 - 2009/1/1

N2 - 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.

AB - 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.

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U2 - 10.1038/ni.1790

DO - 10.1038/ni.1790

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VL - 10

SP - 1185

EP - 1192

JO - Nature Immunology

T2 - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

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ER -

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