Tonsillar CD4+CD25+Regulatory T Cells from IgA Nephropathy Patients Have Decreased Immunosuppressive Activity in Experimental IgA Nephropathy Rats

Background/Aim: 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 x 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)-beta 1 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-beta 1 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. Conclusion: Dysfunction of tonsillar CD4+CD25+ Treg cells may be an important cause of IgAN progression. Copyright (C) 2013 S. Karger AG, Basel