Altered availability of PD-1/PD ligands is associated with the failure to control autoimmunity in NOD mice

Deepak Yadav, Natasha Hill, Hideo Yagita, Miyuki Azuma, Nora Sarvetnick

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Costimulation via the PD-1 and B7-H1/B7-DC pathway regulates immunity. We investigated whether the PD-1/PD-L pathway is impaired in autoimmune diabetes. A progressive increase in the expression of PD-1 and B7-H1/B7-DC on T cells and APC, respectively, was observed in the pancreatic lymph nodes of female non-obese diabetic (NOD) mice as they developed diabetes. A significantly decreased expression of PD-1 and B7-H1/B7-DC on T cells and APC, respectively, was observed in the periphery of prediabetic NOD mice versus non-diabetic C57BL/6 strain. NOD islets also displayed a reduced capacity to upregulate B7-H1 following exposure to inflammatory cytokines. In vivo blocking studies in NOD/B7-2KONOD mice revealed that B7-H1 and B7-DC positively costimulate autoreactive CD4 and CD8 T cells and may co-operate with B7-2 to augment priming and expansion of naïve autoreactive T cells. In summary, these data suggest that diabetes susceptibility in NOD mice is associated with altered PD-1/PD-L availability.

Original languageEnglish (US)
Pages (from-to)161-171
Number of pages11
JournalCellular Immunology
Volume258
Issue number2
DOIs
StatePublished - Jun 5 2009

Fingerprint

Inbred NOD Mouse
Autoimmunity
Ligands
T-Lymphocytes
Type 1 Diabetes Mellitus
Immunity
Up-Regulation
Lymph Nodes
Cytokines

Keywords

  • Autoimmunity
  • B7-DC
  • B7-H1
  • Costimulation
  • Diabetes
  • PD-1

ASJC Scopus subject areas

  • Immunology

Cite this

Altered availability of PD-1/PD ligands is associated with the failure to control autoimmunity in NOD mice. / Yadav, Deepak; Hill, Natasha; Yagita, Hideo; Azuma, Miyuki; Sarvetnick, Nora.

In: Cellular Immunology, Vol. 258, No. 2, 05.06.2009, p. 161-171.

Research output: Contribution to journalArticle

Yadav, Deepak ; Hill, Natasha ; Yagita, Hideo ; Azuma, Miyuki ; Sarvetnick, Nora. / Altered availability of PD-1/PD ligands is associated with the failure to control autoimmunity in NOD mice. In: Cellular Immunology. 2009 ; Vol. 258, No. 2. pp. 161-171.
@article{a681ed153bc44f3abe25cdfa3470e389,
title = "Altered availability of PD-1/PD ligands is associated with the failure to control autoimmunity in NOD mice",
abstract = "Costimulation via the PD-1 and B7-H1/B7-DC pathway regulates immunity. We investigated whether the PD-1/PD-L pathway is impaired in autoimmune diabetes. A progressive increase in the expression of PD-1 and B7-H1/B7-DC on T cells and APC, respectively, was observed in the pancreatic lymph nodes of female non-obese diabetic (NOD) mice as they developed diabetes. A significantly decreased expression of PD-1 and B7-H1/B7-DC on T cells and APC, respectively, was observed in the periphery of prediabetic NOD mice versus non-diabetic C57BL/6 strain. NOD islets also displayed a reduced capacity to upregulate B7-H1 following exposure to inflammatory cytokines. In vivo blocking studies in NOD/B7-2KONOD mice revealed that B7-H1 and B7-DC positively costimulate autoreactive CD4 and CD8 T cells and may co-operate with B7-2 to augment priming and expansion of na{\"i}ve autoreactive T cells. In summary, these data suggest that diabetes susceptibility in NOD mice is associated with altered PD-1/PD-L availability.",
keywords = "Autoimmunity, B7-DC, B7-H1, Costimulation, Diabetes, PD-1",
author = "Deepak Yadav and Natasha Hill and Hideo Yagita and Miyuki Azuma and Nora Sarvetnick",
year = "2009",
month = "6",
day = "5",
doi = "10.1016/j.cellimm.2009.04.006",
language = "English (US)",
volume = "258",
pages = "161--171",
journal = "Cellular Immunology",
issn = "0008-8749",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Altered availability of PD-1/PD ligands is associated with the failure to control autoimmunity in NOD mice

AU - Yadav, Deepak

AU - Hill, Natasha

AU - Yagita, Hideo

AU - Azuma, Miyuki

AU - Sarvetnick, Nora

PY - 2009/6/5

Y1 - 2009/6/5

N2 - Costimulation via the PD-1 and B7-H1/B7-DC pathway regulates immunity. We investigated whether the PD-1/PD-L pathway is impaired in autoimmune diabetes. A progressive increase in the expression of PD-1 and B7-H1/B7-DC on T cells and APC, respectively, was observed in the pancreatic lymph nodes of female non-obese diabetic (NOD) mice as they developed diabetes. A significantly decreased expression of PD-1 and B7-H1/B7-DC on T cells and APC, respectively, was observed in the periphery of prediabetic NOD mice versus non-diabetic C57BL/6 strain. NOD islets also displayed a reduced capacity to upregulate B7-H1 following exposure to inflammatory cytokines. In vivo blocking studies in NOD/B7-2KONOD mice revealed that B7-H1 and B7-DC positively costimulate autoreactive CD4 and CD8 T cells and may co-operate with B7-2 to augment priming and expansion of naïve autoreactive T cells. In summary, these data suggest that diabetes susceptibility in NOD mice is associated with altered PD-1/PD-L availability.

AB - Costimulation via the PD-1 and B7-H1/B7-DC pathway regulates immunity. We investigated whether the PD-1/PD-L pathway is impaired in autoimmune diabetes. A progressive increase in the expression of PD-1 and B7-H1/B7-DC on T cells and APC, respectively, was observed in the pancreatic lymph nodes of female non-obese diabetic (NOD) mice as they developed diabetes. A significantly decreased expression of PD-1 and B7-H1/B7-DC on T cells and APC, respectively, was observed in the periphery of prediabetic NOD mice versus non-diabetic C57BL/6 strain. NOD islets also displayed a reduced capacity to upregulate B7-H1 following exposure to inflammatory cytokines. In vivo blocking studies in NOD/B7-2KONOD mice revealed that B7-H1 and B7-DC positively costimulate autoreactive CD4 and CD8 T cells and may co-operate with B7-2 to augment priming and expansion of naïve autoreactive T cells. In summary, these data suggest that diabetes susceptibility in NOD mice is associated with altered PD-1/PD-L availability.

KW - Autoimmunity

KW - B7-DC

KW - B7-H1

KW - Costimulation

KW - Diabetes

KW - PD-1

UR - http://www.scopus.com/inward/record.url?scp=67649313321&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649313321&partnerID=8YFLogxK

U2 - 10.1016/j.cellimm.2009.04.006

DO - 10.1016/j.cellimm.2009.04.006

M3 - Article

C2 - 19497561

AN - SCOPUS:67649313321

VL - 258

SP - 161

EP - 171

JO - Cellular Immunology

JF - Cellular Immunology

SN - 0008-8749

IS - 2

ER -