T Cells Exacerbate Podocyte Injury via the CD28/B7-1-Phosphor-SRC Kinase Pathway.

Primary nephrotic syndrome (PNS) is a devastating pediatric disorder. However, its mechanism remains unclear. Previous studies detected B7-1 in podocytes; meanwhile, T cells play pivotal roles in immune diseases. Therefore, this study aimed to assess whether and how T cells impact podocytes via the CD28/B7-1 pathway. WT and TCR mice were assessed. LPS was used to induce nephropathy. Total T and CD28T cells were quantitated in mouse spleen and kidney samples. B7-1 and phosphor-SRC levels in the kidney were detected as well. In vitro, T cells from the mouse spleen were cocultured with mouse podocytes, and apoptosis rate and phosphor-SRC expression in podocytes were assessed. Compared with control mice, WT mice with LPS nephropathy showed increased amounts of T cells in the kidney. Kidney injury was alleviated in TCR mice. Meanwhile, B7-1 and phosphor-SRC levels were increased in the kidney from WT mice with LPS nephropathy. CD28T cells were decreased, indicating CD28 may play a role in LPS nephropathy. Immunofluorescence colocalization analysis revealed a tight association of T cells with B7-1 in the kidney. High B7-1 expression was detected in podocytes treated with LPS. Podocytes cocultured with T cells showed higher phosphor-SRC and apoptosis rate than other cell groups. Furthermore, CD28/B7-1 blockage with CTLA4-Ig in vitro relieved podocyte injury. T cells exacerbate podocyte injury via CD28/B7-1 signaling, with downstream involvement of phosphor-SRC. The CD28/B7-1 blocker CTLA4-Ig prevented progressive podocyte injury, providing a potential therapeutic tool for PNS.