PD-L1-deficient mice show that PD-L1 on T cells, antigen-presenting cells, and host tissues negatively regulates T cells

Proceedings of the National Academy of Sciences of the United States of America
Yvette E LatchmanArlene H Sharpe

Abstract

Both positive and negative regulatory roles have been suggested for the B7 family member PD-L1(B7-H1). PD-L1 is expressed on antigen-presenting cells (APCs), activated T cells, and a variety of tissues, but the functional significance of PD-L1 on each cell type is not yet clear. To dissect the functions of PD-L1 in vivo, we generated PD-L1-deficient (PD-L1(-/-)) mice. CD4(+) and CD8(+) T cell responses were markedly enhanced in PD-L1(-/-) mice compared with wild-type mice in vitro and in vivo. PD-L1(-/-) dendritic cells stimulated greater wild-type CD4(+) T cell responses than wild-type dendritic cells, and PD-L1(-/-) CD4(+) T cells produced more cytokines than wild-type CD4(+) T cells in vitro, demonstrating an inhibitory role for PD-L1 on APCs and T cells. In vivo CD8(+) T cell responses also were significantly enhanced, indicating that PD-L1 has a role in limiting the expansion or survival of CD8(+) T cells. Studies using the myelin oligodendrocyte model of experimental autoimmune encephalomyelitis showed that PD-L1 on T cells and in host tissues limits responses of self-reactive CD4(+) T cells in vivo. PD-L1 deficiency converted the 129S4/SvJae strain from a resistant to experimental autoimmune encephalomyelitis-susceptible...Continue Reading

References

Feb 27, 2001·Nature Immunology·Y LatchmanG J Freeman
May 23, 2001·Current Biology : CB·O LechnerJ Buer
Feb 22, 2002·European Journal of Immunology·LauraL CarterBeatriz M Carreno
Apr 5, 2002·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Michael J EppihimerJohn P Leonard
Sep 10, 2002·Proceedings of the National Academy of Sciences of the United States of America·Yoshiko IwaiNagahiro Minato
Oct 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Adam P KohmStephen D Miller
Nov 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tomohide YamazakiHideo Yagita
Dec 10, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christopher C DascherMichael B Brenner
Jan 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Julia A BrownGordon J Freeman
Feb 6, 2003·The Journal of Clinical Investigation·Haidong DongLieping Chen
Apr 30, 2003·The Journal of Experimental Medicine·Shengdian WangLieping Chen
Jul 9, 2003·The Journal of Experimental Medicine·Yoshiko IwaiTasuku Honjo
Jul 9, 2003·The Journal of Experimental Medicine·Mohammed Javeed I AnsariMohamed H Sayegh
Jul 9, 2003·The Journal of Experimental Medicine·Alan D SalamaSamia J Khoury
Sep 30, 2003·European Journal of Immunology·Spencer C LiangArlene H Sharpe
Oct 28, 2003·European Journal of Immunology·Nancy RodigGordon J Freeman

❮ Previous
Next ❯

Citations

Jan 13, 2010·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Heather A Arnett, Joanne L Viney
Feb 25, 2009·Cancer Immunology, Immunotherapy : CII·Joseph Lustgarten
Jan 18, 2011·Cancer Immunology, Immunotherapy : CII·Kevin DurganYvette E Latchman
Feb 4, 2012·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Demelza J IrelandManfred W Beilharz
Jun 12, 2013·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Galina V ShurinMichael R Shurin
Jan 5, 2011·Protein & Cell·Yong ChenGeorge F Gao
Jun 15, 2005·International Immunopharmacology·Yongwen ChenYuzhang Wu
Apr 24, 2012·Cellular & Molecular Immunology·Daniel SilbermanJames E Riggs
Dec 24, 2008·Immunology and Cell Biology·Joanna B TierneyAnne Camille La Flamme
Nov 17, 2010·Immunology and Cell Biology·Stacey AllenIan R van Driel
Dec 18, 2012·Nature Immunology·Peter T SageArlene H Sharpe
Feb 18, 2005·Nature Immunology·Abul K Abbas, Arlene H Sharpe
Feb 17, 2007·Nature Immunology·Arlene H SharpeGordon J Freeman
May 27, 2008·Nature Reviews. Immunology·Weiping Zou, Lieping Chen
Jun 27, 2007·Immunology and Cell Biology·Christian LangeFelix Bischof
Jul 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Li WangRandolph J Noelle
Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·David Yin-Wei LinDavid N Garboczi
Jun 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Li-Fen LeeJohn C Lin
Jul 20, 2005·The Journal of Experimental Medicine·Indira GuleriaMohamed H Sayegh
Apr 12, 2006·The Journal of Experimental Medicine·Mary E KeirArlene H Sharpe
Dec 17, 2009·The Journal of Experimental Medicine·Loise M FranciscoArlene H Sharpe
Mar 9, 2011·The Journal of Experimental Medicine·Li WangRandolph J Noelle
Dec 12, 2012·The Journal of Experimental Medicine·Helge FrebelAnnette Oxenius
Aug 18, 2009·International Immunology·Songwen JuXueguang Zhang
Oct 28, 2005·Biology of Reproduction·Lesya M HoletsMargaret G Petroff
Jun 14, 2008·Biology of Reproduction·Elizabeth S TaglauerMargaret G Petroff
May 29, 2012·Journal of Neuro-ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society·Caroline W ShamLynn K Gordon
Mar 24, 2009·Annual Review of Immunology·Yasmine Belkaid, Kristin Tarbell
Mar 18, 2005·Annual Review of Immunology·Rebecca J GreenwaldArlene H Sharpe
Jan 5, 2008·Annual Review of Immunology·Mary E KeirArlene H Sharpe
Feb 8, 2006·Annual Review of Physiology·Viviany R TaquetiAndrew H Lichtman
Oct 12, 2010·American Journal of Physiology. Lung Cellular and Molecular Physiology·Fatoumata B SowMark R Ackermann
Nov 12, 2005·Nephron. Experimental Nephrology·Yongwen ChenYuzhang Wu
Nov 3, 2007·Kidney & Blood Pressure Research·Ying Waeckerle-MenRudolf P Wüthrich
Nov 26, 2008·Circulation Research·Israel GotsmanAndrew H Lichtman
Apr 23, 2003·American Journal of Respiratory Cell and Molecular Biology·Shin KurosawaRobert P Schleimer
May 23, 2003·American Journal of Respiratory Cell and Molecular Biology·Ryan E WileyManel Jordana
Sep 15, 2007·The Journal of Clinical Investigation·Israel GotsmanAndrew H Lichtman

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.