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J Immunol. 2010 Sep 1;185(5):2800-7. doi: 10.4049/jimmunol.1000856. Epub 2010 Jul 30.

B1 cells promote pancreas infiltration by autoreactive T cells.

Author information

1
Medical Research Council Center for Immune Regulation, University of Birmingham Medical School, Birmingham, United Kingdom.

Abstract

The entry of autoreactive T cells into the pancreas is a critical checkpoint in the development of autoimmune diabetes. In this study, we identify a role for B1 cells in this process using the DO11 x RIP-mOVA mouse model. In transgenic mice with islet-specific T cells, but no B cells, T cells are primed in the pancreatic lymph node but fail to enter the pancreas. Reconstitution of the B1 cell population by adoptive transfer permits extensive T cell pancreas infiltration. Reconstituted B1 cells traffic to the pancreas and modify expression of adhesion molecules on pancreatic vasculature, notably VCAM-1. Despite substantial pancreas infiltration, islet destruction is minimal unless regulatory T cells are depleted. These data identify a role for B1 cells in permitting circulating islet-specific T cells to access their Ag-bearing tissue and emphasize the existence of multiple checkpoints to regulate autoimmune disease.

PMID:
20675587
PMCID:
PMC3983558
DOI:
10.4049/jimmunol.1000856
[Indexed for MEDLINE]
Free PMC Article

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