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Cell Immunol. 2009;258(2):161-71. doi: 10.1016/j.cellimm.2009.04.006. Epub 2009 May 6.

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

Author information

1
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, United States. dyadav@ucsd.edu

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.

PMID:
19497561
DOI:
10.1016/j.cellimm.2009.04.006
[Indexed for MEDLINE]

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