title: Inhibition of clonal expansion by Foxp3 expression as a mechanism of controlled T-cell responses and autoimmune disease.
abstract: The essential role of the transcription factor Foxp3 in the development and function of Treg has been well documented. The role of Foxp3 in non-Treg, however, is not fully understood. Emerging evidence indicates that Foxp3 expression is not confined to CD4+CD25+ Treg. The present study shows that in Foxp3 transgenic (Foxp3-Tg) mice, in which the transgene is driven by the lck distal promoter, CD4+CD25- T cells that express the Foxp3 transgene do not upregulate the expression of CD25-, GITR, or CTLA-4, and do not have suppressive function; however, the Foxp3-Tg+CD4+CD25- T cells exhibit significantly reduced proliferative response to TCR engagement. Foxp3-Tg mice are resistant to collagen-induced arthritis via reduced cellular proliferation of activated T cells. These findings indicate that Foxp3 upregulation in activated non-Treg may be a mechanism to suppress immune responses by reduced clonal expansion of activated T cells.
authors.affiliation: Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Linjie
authors.initials: L
authors.lastname: Guo
authors.forename: Jun
authors.initials: J
authors.lastname: Tian
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Marinova
authors.forename: Biao
authors.initials: B
authors.lastname: Zheng
authors.forename: Shuhua
authors.initials: S
authors.lastname: Han
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D011948:Receptors, Antigen, T-Cell