T cell reactivation in acute kidney injury

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Lymphocyte effector responses are a hallmark of inflammatory processes. Past studies have identified CD4 T cells to be crucially involved in both ischemia-reperfusion mediated kidney injury and glomerulonephritis. However, reactivation of these cells in the tissue is necessary to elicit their biological function. The aim of this study is to characterize the reactivation process of effector T cells in the tissue in models of acute kidney injury. First, we aim to identify the antigen presenting cell responsible for tissue reactivation (as opposed to dendritic cells that mediate priming). In this context we will use a novel FACS based approach to investigate in vivo cell conjugates following ischemia-reperfusion injury and an established glomerulonephritis model with a known antigen. Furthermore, we will examine the role of CD4 T cells in the development of a clinically relevant sepsis induced kidney injury model. Secondly, the transcriptome of reactivating T cells will be analyzed using RNAseq technology. For this purpose, different characteristics of reactivating T cells will be assessed and correlated to identify reactivated T cells. The results of this transcriptome analysis will then be examined in ischemia-reperfusion injury, sepsis induced kidney injury and glomerulonephritis and, in addition, in their dependency on costimulatory molecules and their association with molecules known to be involved in T cell exhaustion. Thirdly, the importance of myeloid cells for reactivation in the tissue will be examined using antibody depletion studies and knockout mice previously reported to have impaired myeloid cell recruitment but intact T cell recruitment.