Mark R Rigby
Wells Center in Diabetes Research,
Riley Hospital for Children, 705 Riley Hospital Drive, ROC 4270, Indianapolis, IN 46202
Tanzania
Research Article
Differential Impact of Costimulation Blockade on Antigen-Activation of Foxp3-Positive and Negative T Cells in A Model of Type 1 Diabetes
Author(s): Mark R Rigby, Alison Trexler, Danxia Duan, Leslie Kean and Christian P LarsenMark R Rigby, Alison Trexler, Danxia Duan, Leslie Kean and Christian P Larsen
Using co stimulatory blockade to prevent activation and activity of beta cell specific effector T cells is a promising approach for preventing or reversing Type 1 diabetes (T1D). Regulatory T cells are likely critical for the maintenance of long-term tolerance. At present, it is unclear how co-stimulatory blocking agents affect the activity of regulatory T cells. To better understand the mechanism of costimulation blockade induced tolerance in murine autoimmune diabetes, we evaluated the effect of CD28 and CD154 blockade on both beta cell-specific effector and regulatory T cell responses.
Diabetes transferred by lymphocytes isolated from BDC2.5.NOD mice could be prevented if cells were antigenactivated ex vivo in the presence of CTLA4Ig and anti- CD154. Following antigen-stimulation, both effector (Teffs; FoxP3-) and regulatory (Tregs; FoxP3+) CD4+ T cells upregulated CD25, di.. View More»
