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

doi:10.1016/j.cellimm.2009.04.006

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

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

Authors

Deepak Yadav¹, Natasha Hill, Hideo Yagita, Miyuki Azuma, Nora Sarvetnick

Affiliation

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

PMID: 19497561
DOI: 10.1016/j.cellimm.2009.04.006

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Animals
Antigen-Presenting Cells / immunology
Antigens, Differentiation / genetics
Antigens, Differentiation / immunology*
Apoptosis Regulatory Proteins
B7-1 Antigen / genetics
B7-1 Antigen / immunology*
B7-H1 Antigen
Diabetes Mellitus, Type 1 / genetics
Diabetes Mellitus, Type 1 / immunology*
Disease Progression
Disease Susceptibility / immunology
Female
Ligands*
Lymph Nodes / immunology
Membrane Glycoproteins / genetics
Membrane Glycoproteins / immunology*
Mice
Mice, Inbred NOD
Mice, Transgenic
Pancreas / immunology
Peptides / genetics
Peptides / immunology*
Programmed Cell Death 1 Ligand 2 Protein
Programmed Cell Death 1 Receptor
Signal Transduction*
Spleen / immunology
T-Lymphocytes / metabolism

Substances

Antigens, Differentiation
Apoptosis Regulatory Proteins
B7-1 Antigen
B7-H1 Antigen
Cd274 protein, mouse
Ligands
Membrane Glycoproteins
Pdcd1 protein, mouse
Pdcd1lg2 protein, mouse
Peptides
Programmed Cell Death 1 Ligand 2 Protein
Programmed Cell Death 1 Receptor