title: Developmental changes of FOXP3-expressing CD4+CD25+ regulatory T cells and their impairment in patients with FOXP3 gene mutations.
abstract: FOXP3 is required for the generation and function of CD4(+)CD25(+) regulatory T (Treg) cells. To elucidate the biological role of Treg cells, we used a monoclonal anti-FOXP3 antibody to examine the frequencies of Treg cells during child development. The percentages of CD4(+)CD25(+)FOXP3(+) T cells were constant shortly from after birth through adulthood. CD4(+)CD25(+)FOXP3(+) T cells in cord blood showed the naive CD45RA(+)CD45RO(-) phenotype, whereas adult CD4(+)CD25(+)FOXP3(+) T cells expressed mostly the memory CD45RA(-)CD45RO(+) phenotype. The age-dependent dominance of memory CD4(+)CD25(+)FOXP3(+) T cells implies functional differences between naive and memory Treg cells. Notably, four patients with FOXP3 gene mutations revealed a paucity of CD4(+)CD25(+)FOXP3(+) T cells. Importantly, one patient with a frame shift mutation, who showed typical symptoms of IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked), exhibited marked T cell activation, whereas others with missense mutations, who were clinically milder, did not. This observation suggests a possible genotype-phenotype correlation in IPEX.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fuchizawa
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Adachi
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Ito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Higashiyama
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kanegane
authors.forename: Takeshi
authors.initials: T
authors.lastname: Futatani
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kobayashi
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Kamachi
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Ikuya
authors.initials: I
authors.lastname: Tsuge
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Alison H
authors.initials: AH
authors.lastname: Banham
authors.forename: Hans D
authors.initials: HD
authors.lastname: Ochs
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyawaki
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007107:Immune System / Q000254:growth & development*; D007156:Immunologic Memory; D007223:Infant; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D009154:Mutation; D010641:Phenotype; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors