Scurfin (FoxP3) Controls T-Dependent Immune Responses In Vivo Through Regulation of CD4+ T Cell Effector Function
- 1 August 2003
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 171 (3), 1216-1223
- https://doi.org/10.4049/jimmunol.171.3.1216
Abstract
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-γ-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.Keywords
This publication has 27 references indexed in Scilit:
- Distinctive characteristics of germinal center B cellsSeminars in Immunology, 1997
- IMMUNE REGULATION BY CD40 AND ITS LIGAND GP39Annual Review of Immunology, 1996
- The CD40L Promoter Contains Nuclear Factor of Activated T Cells-binding Motifs Which Require AP-1 Binding for Activation of TranscriptionPublished by Elsevier BV ,1996
- Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4Science, 1995
- NF-ATp: a transcription factor required for the co-ordinate induction of several cytokine genesImmunology Today, 1994
- A Japanese family of X-linked auto-immune enteropathy with haemolytic anaemia and polyendocrinopathyEuropean Journal of Pediatrics, 1993
- Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory diseaseNature, 1992
- Lymphokine Control of In Vivo Immunoglobulin Isotype SelectionAnnual Review of Immunology, 1990
- TH1 and TH2 Cells: Different Patterns of Lymphokine Secretion Lead to Different Functional PropertiesAnnual Review of Immunology, 1989
- An X-linked syndrome of diarrhea, polyendocrinopathy, and fatal infection in infancyThe Journal of Pediatrics, 1982