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

11 Scopus citations

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 - 2009

Keywords

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

ASJC Scopus subject areas

  • Immunology

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