Scurfin (FoxP3) Controls T-Dependent Immune Responses In Vivo Through Regulation of CD4+ T Cell Effector Function

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 overexp...

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Bibliographic Details
Published in:	The Journal of immunology (1950) Vol. 171; no. 3; pp. 1216 - 1223
Main Authors:	Kasprowicz, Deborah J, Smallwood, P. Scott, Tyznik, Aaron J, Ziegler, Steven F
Format:	Journal Article
Language:	English
Published:	United States Am Assoc Immnol 01-08-2003
Subjects:	Adoptive Transfer Agammaglobulinemia - blood Agammaglobulinemia - genetics Agammaglobulinemia - immunology Animals Antigens, T-Independent - administration & dosage Antigens, T-Independent - immunology B-Lymphocyte Subsets - immunology B-Lymphocyte Subsets - metabolism B-Lymphocyte Subsets - transplantation CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism CD4-Positive T-Lymphocytes - transplantation CD40 Ligand - biosynthesis Cells, Cultured Cytokines - antagonists & inhibitors Cytokines - biosynthesis DNA-Binding Proteins - biosynthesis DNA-Binding Proteins - deficiency DNA-Binding Proteins - genetics DNA-Binding Proteins - physiology Down-Regulation - genetics Down-Regulation - immunology Female Forkhead Transcription Factors Haptens Hemocyanins - administration & dosage Hemocyanins - immunology Immunoglobulin G - biosynthesis Immunoglobulin M - biosynthesis Lymphopenia - genetics Lymphopenia - immunology Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism T-Lymphocyte Subsets - transplantation
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Summary:	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-gamma-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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-1767 1550-6606
DOI:	10.4049/jimmunol.171.3.1216