The PD-1/PD-L1 Pathway Affects the Expansion and Function of Cytotoxic CD8+ T Cells During an Acute Retroviral Infection

Frontiers in Immunology
Paul DavidGennadiy Zelinskyy

Abstract

Cytotoxic CD8+ T lymphocytes (CTL) efficiently control acute virus infections but can become exhausted when a chronic infection develops. The checkpoint receptor PD-1 suppresses the functionality of virus-specific CD8+ T cells during chronic infection. However, the role of the PD-L1/PD-1 pathway during the acute phase of infections has not been well characterized. In the current study the effects of PD-1 or PD-L1 deficiency on the CD8+ T cell response against Friend retroviral (FV) infection of knockout mice was analyzed during acute infection. We observed an enhanced proliferation, functional maturation, and reduced apoptosis of effector CD8+ T cells in the absence of PD-1 or PD-L1. The knockout of PD-L1 had a stronger effect on the functionality of CD8+ T cells than that of PD-1. Augmented CTL responses were associated with an improved control of FV replication. The strong phenotype of FV-infected PD-L1 knockout mice was independent of the interaction with CD80 as an additional receptor for PD-L1. Furthermore, we performed a detailed analysis of the production of different granzymes in virus-specific CD8+ T cells and observed that especially the simultaneous production of multiple granzymes in individual T cells (multifunctio...Continue Reading

References

Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·K J Hasenkrug, B Chesebro
Feb 1, 2000·Journal of Cellular Physiology·T Scholzen, J Gerdes
Dec 1, 2001·The Journal of Biological Chemistry·Susmit SuvasJaved N Agrewala
Sep 10, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Koen SchepersTon N M Schumacher
Jun 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Daniel L BarberRafi Ahmed
Jul 9, 2003·The Journal of Experimental Medicine·Yoshiko IwaiTasuku Honjo
Oct 21, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laurent SabbaghRafick-Pierre Sékaly
Feb 17, 2007·Nature Immunology·Arlene H SharpeGordon J Freeman
Jun 15, 2007·Toxicologic Pathology·Susan Elmore
Feb 29, 2008·Annual Review of Immunology·Dipanjan Chowdhury, Judy Lieberman
May 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Monique LafonHeinz Wiendl
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Apr 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Timothy W PharesCornelia C Bergmann
Mar 31, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shiki TakamuraMasaaki Miyazawa
Jul 20, 2010·Immunological Reviews·Weiguo Cui, Susan M Kaech
Aug 30, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gennadiy ZelinskyyUlf Dittmer
Dec 12, 2012·The Journal of Experimental Medicine·Helge FrebelAnnette Oxenius
Sep 1, 2014·Immunology Letters·Alexandr V BazhinSvetlana Karakhanova
Oct 24, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·John J EricksonJohn V Williams
Jun 3, 2015·The Journal of Experimental Medicine·Pamela M OdorizziE John Wherry
Oct 21, 2015·PLoS Pathogens·Ilseyar AkhmetzyanovaGennadiy Zelinskyy
May 18, 2016·JCI Insight·Roxana S DroncaHaidong Dong

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Citations

May 21, 2020·The Journal of Infectious Diseases·Bruktawit A GoshuMarta Catalfamo
May 7, 2020·Journal of Leukocyte Biology·Olga LeplinaElena Chernykh
Sep 20, 2020·MBio·Jaana WestmeierGennadiy Zelinskyy
Mar 25, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shima ShahbazShokrollah Elahi
Jul 3, 2019·Frontiers in Cellular and Infection Microbiology·Günther Schönrich, Martin J Raftery
Nov 16, 2020·Scandinavian Journal of Immunology·Abubakar Umar AnkaGholamreza Azizi
Nov 14, 2020·Medicinal Research Reviews·Yuan Tan, Faqin Tang
May 19, 2020·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Anne-Marie C DingemansChandra P Belani

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Methods Mentioned

BETA
flow cytometry

Software Mentioned

Proteome Discoverer
DAVID
Progenesis QI
FACSDiva
Database for Annotation , Visualization , and Integrated Disco...
GraphPad Prism
FlowJo
R script
R Foundation for Statistical Computing
GraphPad

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