title: Tonsillar CD4+CD25+ regulatory T cells from IgA nephropathy patients have decreased immunosuppressive activity in experimental IgA nephropathy rats.
abstract: OBJECTIVE
  CD4+CD25+ regulatory T (Treg) cells are of critical importance for maintenance of tolerance. We showed that the number of CD4+CD25+ Treg cells was significantly lower in tonsils of patients with IgA nephropathy (IgAN); however, the function of tonsillar CD4+CD25+ Treg cells in IgAN has not been reported. The aim of this study was to investigate the effect of tonsillar CD4+CD25+ Treg cells of IgAN patients on experimental IgAN in rats.
  
  
  METHODS
  Tonsillar CD4+CD25+ Treg cells were isolated by magnetic beads. A total of 2 × 10(6) CD4+CD25+ Treg cells were transferred into rats that were previously orally immunized over a period of 14 weeks and subsequently received an injection of BSA into the tail vein on 3 consecutive days. Urine protein and erythrocytes were measured. Glomerular injury was assessed by histopathology. Plasminogen activator inhibitor type 1 (PAI-1), interleukin (IL)-6 and transforming growth factor (TGF)-β1 in mesangial cells of rats were examined by reverse transcription PCR. Serum IgA and C3 and supernatants of IL-2, IL-4 and IL-6 in splenic cells were analysed by ELISA. Transferred tonsillar CD4+CD25+ Treg cells were tracked by reverse transcription PCR and flow cytometry.
  
  
  RESULTS
  IgA deposition in the mesangial region and the glomerular planar area and the number of cells, levels of serum IgA and supernatant IL-2, IL-4 and IL-6 in splenic cells and PAI-1, IL-6 and TGF-β1 expression in renal mesangial cells of rats that received CD4+CD25+ Treg cells from IgAN patients were significantly higher than in rats that received CD4+CD25+ Treg cells from the control group, although they were dramatically lower compared with rats treated without CD4+CD25+ Treg cells. Transferred tonsillar CD4+CD25+ Treg cells migrated predominantly to secondary lymphoid organs but not to the kidneys.
  
  
  CONCLUSIONS
  Dysfunction of tonsillar CD4+CD25+ Treg cells may be an important cause of IgAN progression.
authors: Division of Nephrology, Beijing Shijitan Hospital, Capital Medical University, Beijing, PR China. huanghd1126@126.com
authors: Hongdong
authors: H
authors: Huang
authors: Youming
authors: Y
authors: Peng
authors: Xi-Dai
authors: XD
authors: Long
authors: Zhihua
authors: Z
authors: Liu
authors: Xiaojun
authors: X
authors: Wen
authors: Meng
authors: M
authors: Jia
authors: Yumei
authors: Y
authors: Liang
authors: Anlan
authors: A
authors: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D003176:Complement C3 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005922:Glomerulonephritis, IGA / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007108:Immune Tolerance; D008297:Male; D014066:Palatine Tonsil / Q000276:immunology* / Q000473:pathology; D051381:Rats; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D055815:Young Adult
chemical_list: D003176:Complement C3