PD-1 upregulated on regulatory T cells during chronic virus infection enhances the suppression of CD8+ T cell immune response via the interaction with PD-L1 expressed on CD8+ T cells

Hyo Jin Park, Joon Seok Park, Yun Hee Jeong, Jimin Son, Young Ho Ban, Byoung Hee Lee, Lieping Chen, Jun Chang, Doo Hyun Chung, Inhak Choi, Sang Jun Ha

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Regulatory T (Treg) cells act as terminators of T cell immuniy during acute phase of viral infection; however, their role and suppressive mechanism in chronic viral infection are not completely understood. In this study, we compared the phenotype and function of Treg cells during acute or chronic infection with lymphocytic choriomeningitis virus. Chronic infection, unlike acute infection, led to a large expansion of Treg cells and their upregulation of programmed death-1 (PD-1). Treg cells from chronically infected mice (chronic Treg cells) displayed greater suppressive capacity for inhibiting both CD8+ and CD4+ T cell proliferation and subsequent cytokine production than those from naive or acutely infected mice. A contact between Treg and CD8+ T cells was necessary for the potent suppression of CD8+ T cell immune response. More importantly, the suppression required cell-specific expression and interaction of PD-1 on chronic Treg cells and PD-1 ligand on CD8+ T cells. Our study defines PD-1 upregulated on Treg cells and its interaction with PD-1 ligand on effector T cells as one cause for the potent T cell suppression and proposes the role of PD-1 on Treg cells, in addition to that on exhausted T cells, during chronic viral infection.

Original languageEnglish
Pages (from-to)5801-5811
Number of pages11
JournalJournal of Immunology
Volume194
Issue number12
DOIs
Publication statusPublished - 2015 Jun 15

Fingerprint

Virus Diseases
Regulatory T-Lymphocytes
T-Lymphocytes
Infection
Ligands
Lymphocytic choriomeningitis virus
Cell Communication
Cell Death
Up-Regulation
Cell Proliferation
Cytokines
Phenotype

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Park, Hyo Jin ; Park, Joon Seok ; Jeong, Yun Hee ; Son, Jimin ; Ban, Young Ho ; Lee, Byoung Hee ; Chen, Lieping ; Chang, Jun ; Chung, Doo Hyun ; Choi, Inhak ; Ha, Sang Jun. / PD-1 upregulated on regulatory T cells during chronic virus infection enhances the suppression of CD8+ T cell immune response via the interaction with PD-L1 expressed on CD8+ T cells. In: Journal of Immunology. 2015 ; Vol. 194, No. 12. pp. 5801-5811.
@article{c433981993c1436b909a6b34bbc60680,
title = "PD-1 upregulated on regulatory T cells during chronic virus infection enhances the suppression of CD8+ T cell immune response via the interaction with PD-L1 expressed on CD8+ T cells",
abstract = "Regulatory T (Treg) cells act as terminators of T cell immuniy during acute phase of viral infection; however, their role and suppressive mechanism in chronic viral infection are not completely understood. In this study, we compared the phenotype and function of Treg cells during acute or chronic infection with lymphocytic choriomeningitis virus. Chronic infection, unlike acute infection, led to a large expansion of Treg cells and their upregulation of programmed death-1 (PD-1). Treg cells from chronically infected mice (chronic Treg cells) displayed greater suppressive capacity for inhibiting both CD8+ and CD4+ T cell proliferation and subsequent cytokine production than those from naive or acutely infected mice. A contact between Treg and CD8+ T cells was necessary for the potent suppression of CD8+ T cell immune response. More importantly, the suppression required cell-specific expression and interaction of PD-1 on chronic Treg cells and PD-1 ligand on CD8+ T cells. Our study defines PD-1 upregulated on Treg cells and its interaction with PD-1 ligand on effector T cells as one cause for the potent T cell suppression and proposes the role of PD-1 on Treg cells, in addition to that on exhausted T cells, during chronic viral infection.",
author = "Park, {Hyo Jin} and Park, {Joon Seok} and Jeong, {Yun Hee} and Jimin Son and Ban, {Young Ho} and Lee, {Byoung Hee} and Lieping Chen and Jun Chang and Chung, {Doo Hyun} and Inhak Choi and Ha, {Sang Jun}",
year = "2015",
month = "6",
day = "15",
doi = "10.4049/jimmunol.1401936",
language = "English",
volume = "194",
pages = "5801--5811",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "12",

}

PD-1 upregulated on regulatory T cells during chronic virus infection enhances the suppression of CD8+ T cell immune response via the interaction with PD-L1 expressed on CD8+ T cells. / Park, Hyo Jin; Park, Joon Seok; Jeong, Yun Hee; Son, Jimin; Ban, Young Ho; Lee, Byoung Hee; Chen, Lieping; Chang, Jun; Chung, Doo Hyun; Choi, Inhak; Ha, Sang Jun.

In: Journal of Immunology, Vol. 194, No. 12, 15.06.2015, p. 5801-5811.

Research output: Contribution to journalArticle

TY - JOUR

T1 - PD-1 upregulated on regulatory T cells during chronic virus infection enhances the suppression of CD8+ T cell immune response via the interaction with PD-L1 expressed on CD8+ T cells

AU - Park, Hyo Jin

AU - Park, Joon Seok

AU - Jeong, Yun Hee

AU - Son, Jimin

AU - Ban, Young Ho

AU - Lee, Byoung Hee

AU - Chen, Lieping

AU - Chang, Jun

AU - Chung, Doo Hyun

AU - Choi, Inhak

AU - Ha, Sang Jun

PY - 2015/6/15

Y1 - 2015/6/15

N2 - Regulatory T (Treg) cells act as terminators of T cell immuniy during acute phase of viral infection; however, their role and suppressive mechanism in chronic viral infection are not completely understood. In this study, we compared the phenotype and function of Treg cells during acute or chronic infection with lymphocytic choriomeningitis virus. Chronic infection, unlike acute infection, led to a large expansion of Treg cells and their upregulation of programmed death-1 (PD-1). Treg cells from chronically infected mice (chronic Treg cells) displayed greater suppressive capacity for inhibiting both CD8+ and CD4+ T cell proliferation and subsequent cytokine production than those from naive or acutely infected mice. A contact between Treg and CD8+ T cells was necessary for the potent suppression of CD8+ T cell immune response. More importantly, the suppression required cell-specific expression and interaction of PD-1 on chronic Treg cells and PD-1 ligand on CD8+ T cells. Our study defines PD-1 upregulated on Treg cells and its interaction with PD-1 ligand on effector T cells as one cause for the potent T cell suppression and proposes the role of PD-1 on Treg cells, in addition to that on exhausted T cells, during chronic viral infection.

AB - Regulatory T (Treg) cells act as terminators of T cell immuniy during acute phase of viral infection; however, their role and suppressive mechanism in chronic viral infection are not completely understood. In this study, we compared the phenotype and function of Treg cells during acute or chronic infection with lymphocytic choriomeningitis virus. Chronic infection, unlike acute infection, led to a large expansion of Treg cells and their upregulation of programmed death-1 (PD-1). Treg cells from chronically infected mice (chronic Treg cells) displayed greater suppressive capacity for inhibiting both CD8+ and CD4+ T cell proliferation and subsequent cytokine production than those from naive or acutely infected mice. A contact between Treg and CD8+ T cells was necessary for the potent suppression of CD8+ T cell immune response. More importantly, the suppression required cell-specific expression and interaction of PD-1 on chronic Treg cells and PD-1 ligand on CD8+ T cells. Our study defines PD-1 upregulated on Treg cells and its interaction with PD-1 ligand on effector T cells as one cause for the potent T cell suppression and proposes the role of PD-1 on Treg cells, in addition to that on exhausted T cells, during chronic viral infection.

UR - http://www.scopus.com/inward/record.url?scp=84931406088&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84931406088&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1401936

DO - 10.4049/jimmunol.1401936

M3 - Article

C2 - 25934860

AN - SCOPUS:84931406088

VL - 194

SP - 5801

EP - 5811

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 12

ER -