Nuclear antigen-reactive CD4+ T cells expand in active systemic lupus erythematosus, produce effector cytokines, and invade the kidneys.

Dimas Abdirama, Sebastian Tesch, Anna-Sophie Grießbach, Caroline von Spee-Mayer, Jens Y Humrich, Ulrik Stervbo, Nina Babel, Christian Meisel, Tobias Alexander, Robert Biesen, Petra Bacher, Alexander Scheffold, Kai-Uwe Eckardt, Falk Hiepe, Andreas Radbruch, Gerd-Rüdiger Burmester, Gabriela Riemekasten, Philipp Enghard
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Kidney international
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Systemic lupus erythematosus is a systemic and chronic autoimmune disease characterized by loss of tolerance towards nuclear antigens with autoreactive CD4+ T cells implicated in disease pathogenesis. However, very little is known about their receptor specificity since the detection of human autoantigen specific CD4+ T cells has been extremely challenging. Here we present an analysis of CD4+ T cells reactive to nuclear antigens using two complementary methods: T cell libraries and antigen-reactive T cell enrichment. The frequencies of nuclear antigen specific CD4+ T cells correlated with disease severity. These autoreactive T cells produce effector cytokines such as interferon-γ, interleukin-17, and interleukin-10. Compared to blood, these cells were enriched in the urine of patients with active lupus nephritis, suggesting an infiltration of the inflamed kidneys. Thus, these previously unrecognized characteristics support a role for nuclear antigen-specific CD4+ T cells in systemic lupus erythematosus.