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Benaroya Research Institute at Virginia Mason, Seattle, WA 98101
Scurfin, the protein product of the FoxP3 gene, is a forkhead-family transcription factor that negatively regulates T cell function. Mice carrying a loss-of-function mutation in FoxP3 (scurfy mice) present with fatal autoimmune-like disease caused by hyperresponsive CD4+ T cells. Mice that overexpress scurfin (FoxP3 Tg mice) possess fewer mature T cells with reduced functional capabilities compared with normal littermate control mice. We analyzed the ability of CD4+ T cells and B cells from FoxP3 Tg mice to respond to a T-dependent Ag and found that immunized FoxP3 Tg mice displayed reduced total and Ag-specific serum Ig and disorganized splenic architecture. However, when cultured in vitro, FoxP3 Tg B cells responded normally, suggesting that the poor Ab response was a result of defective T cell help in vivo. When challenged, CD4+ T cells from FoxP3 Tg mice display reduced up-regulation of CD40 ligand and fewer IFN-
-producing cells. Overall, these findings show that overexpression of scurfin reduces T cell responses in vivo such that CD4+ T cells cannot provide help to B cells during a T cell-dependent Ab response.
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