Identification and characterization of antigen-specific CD4<sup>+</sup> T cells targeting renally expressed antigens in human lupus nephritis with two independent methods.

Sebastian Tesch, Dimas Abdirama, Anna-Sophie Grießbach, Hannah Antonia Brand, Nina Goerlich, Jens Y Humrich, Petra Bacher, Falk Hiepe, Gabriela Riemekasten, Philipp Enghard
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Scientific Reports
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In the search for anti-renal autoreactivity in human lupus nephritis, we stimulated blood-derived CD4<sup>+</sup> T cells from patients with systemic lupus erythematosus with various kidney lysates. Although only minor responses were detectable, these experiments led to the development of a search algorithm that combined autoantibody association with human lupus nephritis and target gene expression in inflamed kidneys. Applying this algorithm, five potential T cell antigens were identified. Blood-derived CD4<sup>+</sup> T cells were then stimulated with these antigens. The cells were magnetically enriched prior to measurement with flow cytometry to facilitate the detection of very rare autoantigen-specific cells. The detected responses were dominated by IFN-γ-producing CD4<sup>+</sup> T cells. Additionally, IL-10-producing CD4<sup>+</sup> T cells were found. In a next step, T cell reactivity to each single antigen was independently evaluated with T cell libraries and [<sup>3</sup>H]-thymidine incorporation assays. Here, Vimentin and Annexin A2 were identified as the main T cell targets. Finally, Vimentin reactive T cells were also found in the urine of three patients with active disease. Overall, our experiments show that antigen-specific CD4<sup>+</sup> T cells targeting renally expressed antigens arise in human lupus nephritis and correlate with disease activity and are mainly of the Th1 subset.