title: CD4+ FOXP3+ Regulatory T Cells Exhibit Impaired Ability to Suppress Effector T Cell Proliferation in Patients with Turner Syndrome.
abstract: OBJECTIVE
  We investigated whether the frequency, phenotype, and suppressive function of CD4+ FOXP3+ regulatory T cells (Tregs) are altered in young TS patients with the 45,X karyotype compared to age-matched controls.
  
  
  METHODS
  Peripheral blood mononuclear cells from young TS patients (n = 24, 17.4-35.9 years) and healthy controls (n = 16) were stained with various Treg markers to characterize their phenotypes. Based on the presence of thyroid autoimmunity, patients were categorized into TS (-) (n = 7) and TS (+) (n = 17). Tregs sorted for CD4+ CD25bright were co-cultured with autologous CD4+ CD25- target cells in the presence of anti-CD3 and -CD28 antibodies to assess their suppressive function.
  
  
  RESULTS
  Despite a lower frequency of CD4+ T cells in the TS (-) and TS (+) patients (mean 30.8% and 31.7%, vs. 41.2%; P = 0.003 and P < 0.001, respectively), both groups exhibited a higher frequency of FOXP3+ Tregs among CD4+ T cells compared with controls (means 1.99% and 2.05%, vs. 1.33%; P = 0.029 and P = 0.004, respectively). There were no differences in the expression of CTLA-4 and the frequency of Tregs expressing CXCR3+, and CCR4+ CCR6+ among the three groups. However, the ability of Tregs to suppress the in vitro proliferation of autologous CD4+ CD25- T cells was significantly impaired in the TS (-) and TS (+) patients compared to controls (P = 0.003 and P = 0.041). Meanwhile, both the TS (-) and TS (+) groups had lower frequencies of naïve cells (P = 0.001 for both) but higher frequencies of effector memory cells (P = 0.004 and P = 0.002) than did the healthy control group.
  
  
  CONCLUSIONS
  The Tregs of the TS patients could not efficiently suppress the proliferation of autologous effector T cells, despite their increased frequency in peripheral CD4+ T cells.
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.
authors.forename: Young Ah
authors.initials: YA
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.
authors.forename: Hang-Rae
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.
authors.forename: Jeong Seon
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.
authors.forename: Hae Woon
authors.initials: HW
authors.lastname: Jung
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.
authors.forename: Hwa Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.
authors.forename: Gyung Min
authors.initials: GM
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Sim
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.
authors.forename: Sae Jin
authors.initials: SJ
authors.lastname: Oh
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.|Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.|Ischemic/Hypoxia Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.
authors.forename: Choong Ho
authors.initials: CH
authors.lastname: Shin
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.
authors.forename: Sei Won
authors.initials: SW
authors.lastname: Yang
mesh_terms: D000328:Adult; D015704:CD4 Antigens / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000378:metabolism; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014424:Turner Syndrome / Q000276:immunology*; D055815:Young Adult
chemical_list: D015704:CD4 Antigens; D060908:CTLA-4 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors