title: IL-21 production by CD4+ effector T cells and frequency of circulating follicular helper T cells are increased in type 1 diabetes patients.
abstract: OBJECTIVE
  Type 1 diabetes results from the autoimmune destruction of insulin-secreting pancreatic beta cells by T cells. Despite the established role of T cells in the pathogenesis of the disease, to date, with the exception of the identification of islet-specific T effector (Teff) cells, studies have mostly failed to identify reproducible alterations in the frequency or function of T cell subsets in peripheral blood from patients with type 1 diabetes.
  
  
  METHODS
  We assessed the production of the proinflammatory cytokines IL-21, IFN-γ and IL-17 in peripheral blood mononuclear cells from 69 patients with type 1 diabetes and 61 healthy donors. In an additional cohort of 30 patients with type 1 diabetes and 32 healthy donors, we assessed the frequency of circulating T follicular helper (Tfh) cells in whole blood. IL-21 and IL-17 production was also measured in peripheral blood mononuclear cells (PBMCs) from a subset of 46 of the 62 donors immunophenotyped for Tfh.
  
  
  RESULTS
  We found a 21.9% (95% CI 5.8, 40.2; p = 3.9 × 10(-3)) higher frequency of IL-21(+) CD45RA(-) memory CD4(+) Teffs in patients with type 1 diabetes (geometric mean 5.92% [95% CI 5.44, 6.44]) compared with healthy donors (geometric mean 4.88% [95% CI 4.33, 5.50]). Consistent with this finding, we found a 14.9% increase in circulating Tfh cells in the patients (95% CI 2.9, 26.9; p = 0.016).
  
  
  CONCLUSIONS
  These results indicate that increased IL-21 production is likely to be an aetiological factor in the pathogenesis of type 1 diabetes that could be considered as a potential therapeutic target.
authors: JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, WT/MRC Building, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0XY, UK, ricardo.ferreira@cimr.cam.ac.uk.
authors: Ricardo C
authors: RC
authors: Ferreira
authors: Henry Z
authors: HZ
authors: Simons
authors: Whitney S
authors: WS
authors: Thompson
authors: Antony J
authors: AJ
authors: Cutler
authors: Xaquin Castro
authors: XC
authors: Dopico
authors: Deborah J
authors: DJ
authors: Smyth
authors: Meghavi
authors: M
authors: Mashar
authors: Helen
authors: H
authors: Schuilenburg
authors: Neil M
authors: NM
authors: Walker
authors: David B
authors: DB
authors: Dunger
authors: Chris
authors: C
authors: Wallace
authors: John A
authors: JA
authors: Todd
authors: Linda S
authors: LS
authors: Wicker
authors: Marcin L
authors: ML
authors: Pekalski
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: D015415:Biomarkers; C573415:IFNG protein, human; D020381:Interleukin-17; D007378:Interleukins; D007371:Interferon-gamma; D000098546:Interleukin-21
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