Role of the adaptive immune system in glomerulonephritis

The T cell component of the adaptive immune system in glomerulonephritis (GN). Antigen is presented to naïve CD4 T cells by dendritic cells (signal 1). Depending upon the predominant cytokine environment, T cells differentiate into CD4 T cell subsets that play different roles in the pathogenesis of glomerular disease. In the presence of transforming growth factor beta (TGF-β), T regulatory cells (Tregs) develop that make TGF-β, interleukin-10 (IL-10), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) that downregulate and control the immune response. IL-12 stimulates differentiation into Th1 cells that make interferon gamma (IFNγ) and TNF and produce traditional T cell/macrophage-mediated delayed-type hypersensitivity (DTH) reactions. IL-2, IL-4, and IL-13 favor the development of Th2 cells that make IL-4, IL-5, and IL-13, and lead to allergic-type hypersensitivity reactions involving immunoglobulin E (IgE) and eosinophils (Eos). The CD4 T cells most implicated in the pathogenesis of GN are Th17 cells that differentiate in the presence of TGF-β, IL-6, and especially IL-17, and those that produce IL-17a and IL-21 that facilitate recruitment of other inflammatory cells, such as neutrophils (PMNs), and also cause tissue injury directly.