Immune-mediated diseases, such as crescentic glomerulonephritis (cGN), are driven by inappropriately regulated cellular and humoral immune responses leading to renal injury and decline in kidney function. However, mechanisms of immune regulation in cGN are less clear. In a mouse model of cGN, we have shown previously that Foxp3+ regulatory T cells (Tregs) suppress the pathogenic T cell response by production of IL-10. Recently, we demonstrated that the co-inhibitory PD-1/PD-L1 pathway promotes Treg function during cGN, which is crucial to control the inflammatory Th1 immune response. Interestingly, preliminary data suggest that also inflammatory CD8+ T cell responses are regulated by the PD-1/PD-L1 pathway during cGN. However, the phenotype, pathogenic relevance, biological function, and regulation of renal CD8+ T cell responses in cGN are still incompletely understood. Thus, our studies will address the following aims: 1.) Phenotype and function of CD8+ T cells in murine models of acute and chronic cGN. 2.) Regulation of inflammatory T cell responses by the co-inhibitory receptors PD-1 and TIGIT. 3.) Mechanisms of T cell activation and regulation by non-professional APCs from kidney and liver. 4.) Phenotypic characterization of renal CD8+ T cell subsets in cGN patients by single cell RNAseq and immunohistochemistry. Our studies will result in a better understanding of mechanisms involved in the pathology and regulation of local inflammatory immune responses in acute and chronic cGN that may result in the identification of novel therapeutic targets in cGN.