title: Identification of FOXP3-negative regulatory T-like (CD4(+)CD25(+)CD127(low)) cells in patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome.
abstract: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is an autoimmune disorder caused by mutations in the FOXP3 gene, which plays a key role in the generation of CD4(+)CD25(+)regulatory T (Treg) cells. We selected CD127 as the surface marker of Treg cells to illustrate the development and function of Treg cells in IPEX syndrome. CD4(+)CD25(+)FOXP3(+) T cells, the putative Treg cells, were almost completely absent in all patients. Importantly, a substantial number of CD4(+)CD25(+)CD127(low) T cells were observed in 3 IPEX patients with hypomorphic mutations in the FOXP3 gene. We demonstrated that CD4(+)CD25(+)CD127(low) T cells isolated from these 3 patients exhibited an appreciable suppressive activity on effector T cell proliferation, although less than that displayed by Treg cells from healthy controls. These results suggest that genetically altered FOXP3 can drive the generation of functionally immature Treg cells, but that intact FOXP3 is necessary for the complete function of Treg cells.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Otsubo
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kanegane
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Kamachi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kobayashi
authors.forename: Ikuya
authors.initials: I
authors.lastname: Tsuge
authors.forename: Masue
authors.initials: M
authors.lastname: Imaizumi
authors.forename: Yoji
authors.initials: Y
authors.lastname: Sasahara
authors.forename: Akira
authors.initials: A
authors.lastname: Hayakawa
authors.forename: Kandai
authors.initials: K
authors.lastname: Nozu
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Iijima
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ito
authors.forename: Reiko
authors.initials: R
authors.lastname: Horikawa
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nagai
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takatsu
authors.forename: Hisashi
authors.initials: H
authors.lastname: Mori
authors.forename: Hans D
authors.initials: HD
authors.lastname: Ochs
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyawaki
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D051858:Forkhead Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000276:immunology*; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D009154:Mutation; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D013577:Syndrome; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000276:immunology* / Q000473:pathology; D055815:Young Adult
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053699:Interleukin-7 Receptor alpha Subunit