Abdirama Dimas, Tesch Sebastian, Grießbach Anna-Sophie, von Spee-Mayer Caroline, Humrich Jens Y, Stervbo Ulrik, Babel Nina, Meisel Christian, Alexander Tobias, Biesen Robert, Bacher Petra, Scheffold Alexander, Eckardt Kai-Uwe, Hiepe Falk, Radbruch Andreas, Burmester Gerd-Rüdiger, Riemekasten Gabriela, Enghard Philipp
Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Deutsches Rheuma-Forschungszentrum, a Leibniz Institute, Berlin, Germany.
Center for Chronic Immunodeficiency, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Kidney Int. 2021 Jan;99(1):238-246. doi: 10.1016/j.kint.2020.05.051. Epub 2020 Jun 24.
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.
系统性红斑狼疮是一种全身性慢性自身免疫性疾病，其特征是对核抗原失去耐受性，自身反应性CD4 T细胞参与疾病发病机制。然而，由于检测人类自身抗原特异性CD4 T细胞极具挑战性，关于它们的受体特异性知之甚少。在此，我们使用两种互补方法对反应于核抗原的CD4 T细胞进行分析：T细胞文库和抗原反应性T细胞富集。核抗原特异性CD4 T细胞的频率与疾病严重程度相关。这些自身反应性T细胞产生效应细胞因子，如干扰素-γ、白细胞介素-17和白细胞介素-10。与血液相比，这些细胞在活动性狼疮性肾炎患者的尿液中富集，提示炎症肾脏有浸润。因此，这些先前未被认识的特征支持核抗原特异性CD4 T细胞在系统性红斑狼疮中的作用。
