Follicular Helper T Cells and Follicular Regulatory T Cells Involved in Immune Disorders of Idiopathic Membranous Nephropathy

Abstract

Objectives: To investigate the role of follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells in immune disorders of idiopathic membranous nephropathy (IMN).

Methods: Peripheral blood samples of 41 IMN patients and 30 healthy controls were collected. The percentages of B cells, Tfh cells and Tfr cells were determined by flow cytometry, and the concentrations of IL-6, IL-17A, and IL-21 were determined by enzyme linked immunosorbent assay (ELISA). Furthermore, sorted Tfh cells or Tfr cells were co-cultured with B cells in vitro to detect the cell function.

Results: B cells, Tfh cells, Tfr cells, Tfr / Tfh ratio, IL-6, IL-17A, and IL-21 were significantly higher in IMN patients compared to controls. IMN patients had reduced percentages of CTLA-4+Tfr cells, increased percentages of PD-1+Tfr cells, and reduced CTLA-4+Tfr / PD-1+Tfr. In the co-culture system, IgG4, lactic acid, IL-6, IL-17A, and IL-21 were higher in Tfh cells derived from IMN patients, while IgG4, lactic acid, IL-6, IL-17A, and IL-21 were lower in Tfr cells derived from healthy patients.

Conclusions: Tfh cells and Tfr cells are involved in immune disorders in IMN. This may be associated with abnormal expression of CTLA-4 and PD-1.

Keywords: B cells; Follicular helper T; Follicular regulatory T; Idiopathic membranous nephropathy; IgG4.