TY - JOUR
T1 - B1 cells promote pancreas infiltration by autoreactive T cells
AU - Ryan, Gemma A
AU - Wang, Chun Jing
AU - Chamberlain, Jayne L.
AU - Attridge, Kesley
AU - Schmidt, Emily M.
AU - Kenefeck, Rupert
AU - Clough, Louise E.
AU - Dunussi-Joannopoulos, Kyri
AU - Toellner, Kai-Michael
AU - Walker, Lucy S.K.
PY - 2010/9/1
Y1 - 2010/9/1
N2 - 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.
AB - 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.
KW - adoptive transfer
KW - autoimmune diseases
KW - B-lymphocyte subsets
KW - CD8-positive T-lymphocytes
KW - cell movement
KW - diabetes mellitus
KW - islets of Langerhans
KW - lymphocyte depletion
KW - ovalbumin
KW - vascular cell adhesion molecule-1
UR - http://www.jimmunol.org/content/185/5/2800
U2 - 10.4049/jimmunol.1000856
DO - 10.4049/jimmunol.1000856
M3 - Article
C2 - 20675587
SN - 0022-1767
VL - 185
SP - 2800
EP - 2807
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -