title: The amount of scurfin protein determines peripheral T cell number and responsiveness.
abstract: In the absence of the recently identified putative transcription factor scurfin, mice develop a lymphoproliferative disorder resulting in death by 3 wk of age from a pathology that resembles TGF-beta or CTLA-4 knockout mice. In this report, we characterize mice that overexpress the scurfin protein and demonstrate that these animals have a dramatically depressed immune system. Mice transgenic for the Foxp3 gene (which encodes the scurfin protein) have fewer T cells than their littermate controls, and those T cells that remain have poor proliferative and cytolytic responses and make little IL-2 after stimulation through the TCR. Although thymic development appears normal in these mice, peripheral lymphoid organs, particularly lymph nodes, are relatively acellular. In a separate transgenic line, forced expression of the gene specifically in the thymus can alter thymic development; however, this does not appear to affect peripheral T cells and is unable to prevent disease in mice lacking a functional Foxp3 gene, indicating that the scurfin protein acts on peripheral T cells. The data indicate a critical role for the Foxp3 gene product in the function of the immune system, with both the number and functionality of peripheral T cells under the aegis of the scurfin protein.
authors.affiliation: Celltech R&D, Inc., Bothell, WA 98021, USA.
authors.forename: R
authors.initials: R
authors.lastname: Khattri
authors.forename: D
authors.initials: D
authors.lastname: Kasprowicz
authors.forename: T
authors.initials: T
authors.lastname: Cox
authors.forename: M
authors.initials: M
authors.lastname: Mortrud
authors.forename: M W
authors.initials: MW
authors.lastname: Appleby
authors.forename: M E
authors.initials: ME
authors.lastname: Brunkow
authors.forename: S F
authors.initials: SF
authors.lastname: Ziegler
authors.forename: F
authors.initials: F
authors.lastname: Ramsdell
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation / Q000276:immunology; D006651:Histocytochemistry; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology; D018655:Lymphocyte Count; D007959:Lymphocyte Culture Test, Mixed; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019076:Transgenes / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse