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

doi:10.1016/j.kint.2020.05.051

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

^*Corresponding author for this work

Clinic of Rheumatology

2 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Kidney International
ISSN	0085-2538
DOIs	https://doi.org/10.1016/j.kint.2020.05.051
Publication status	Published - 24.06.2020

Funding

We thank Toralf Kaiser and Jenny Kirsch (Flow Cytometry and Cell Sorting Facility, Deutsches Rheuma-Forschungszentrum Berlin) for assistance with flow cytometry and cell sorting. Support for these studies was provided by grants from the Deutsche Forschungsgemeinschaft within the Sonderforschungsbereich 650 to GR and by grants from Deutsche Gesellschaft für Nephrologie and Clinical Scientist Program of Charité – Universitätsmedizin Berlin and Berlin Institute of Health to PE.

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.kint.2020.05.051

Cite this

Abdirama, D., Tesch, S., Grießbach, A. S., von Spee-Mayer, C., Humrich, J. Y., Stervbo, U., Babel, N., Meisel, C., Alexander, T., Biesen, R., Bacher, P., Scheffold, A., Eckardt, K. U., Hiepe, F., Radbruch, A., Burmester, G. R., Riemekasten, G., & Enghard, P. (2020). Nuclear antigen–reactive CD4⁺ T cells expand in active systemic lupus erythematosus, produce effector cytokines, and invade the kidneys. Kidney International. https://doi.org/10.1016/j.kint.2020.05.051

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title = "Nuclear antigen–reactive CD4+ T cells expand in active systemic lupus erythematosus, produce effector cytokines, and invade the kidneys",

abstract = "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.",

author = "Dimas Abdirama and Sebastian Tesch and Grie{\ss}bach, {Anna Sophie} and {von Spee-Mayer}, Caroline and Humrich, {Jens Y.} and Ulrik Stervbo and Nina Babel and Christian Meisel and Tobias Alexander and Robert Biesen and Petra Bacher and Alexander Scheffold and Eckardt, {Kai Uwe} and Falk Hiepe and Andreas Radbruch and Burmester, {Gerd R{\"u}diger} and Gabriela Riemekasten and Philipp Enghard",

note = "Funding Information: We thank Toralf Kaiser and Jenny Kirsch (Flow Cytometry and Cell Sorting Facility, Deutsches Rheuma-Forschungszentrum Berlin) for assistance with flow cytometry and cell sorting. Support for these studies was provided by grants from the Deutsche Forschungsgemeinschaft within the Sonderforschungsbereich 650 to GR and by grants from Deutsche Gesellschaft f{\"u}r Nephrologie and Clinical Scientist Program of Charit{\'e} – Universit{\"a}tsmedizin Berlin and Berlin Institute of Health to PE. Publisher Copyright: {\textcopyright} 2020 International Society of Nephrology Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2020",

month = jun,

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doi = "10.1016/j.kint.2020.05.051",

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Abdirama, D, Tesch, S, Grießbach, AS, von Spee-Mayer, C, Humrich, JY, Stervbo, U, Babel, N, Meisel, C, Alexander, T, Biesen, R, Bacher, P, Scheffold, A, Eckardt, KU, Hiepe, F, Radbruch, A, Burmester, GR, Riemekasten, G & Enghard, P 2020, 'Nuclear antigen–reactive CD4⁺ T cells expand in active systemic lupus erythematosus, produce effector cytokines, and invade the kidneys', Kidney International. https://doi.org/10.1016/j.kint.2020.05.051

TY - JOUR

T1 - Nuclear antigen–reactive CD4+ T cells expand in active systemic lupus erythematosus, produce effector cytokines, and invade the kidneys

AU - Abdirama, Dimas

AU - Tesch, Sebastian

AU - Grießbach, Anna Sophie

AU - von Spee-Mayer, Caroline

AU - Humrich, Jens Y.

AU - Stervbo, Ulrik

AU - Babel, Nina

AU - Meisel, Christian

AU - Alexander, Tobias

AU - Biesen, Robert

AU - Bacher, Petra

AU - Scheffold, Alexander

AU - Eckardt, Kai Uwe

AU - Hiepe, Falk

AU - Radbruch, Andreas

AU - Burmester, Gerd Rüdiger

AU - Riemekasten, Gabriela

AU - Enghard, Philipp

N1 - Funding Information: We thank Toralf Kaiser and Jenny Kirsch (Flow Cytometry and Cell Sorting Facility, Deutsches Rheuma-Forschungszentrum Berlin) for assistance with flow cytometry and cell sorting. Support for these studies was provided by grants from the Deutsche Forschungsgemeinschaft within the Sonderforschungsbereich 650 to GR and by grants from Deutsche Gesellschaft für Nephrologie and Clinical Scientist Program of Charité – Universitätsmedizin Berlin and Berlin Institute of Health to PE. Publisher Copyright: © 2020 International Society of Nephrology Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/6/24

Y1 - 2020/6/24

N2 - 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.

AB - 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.

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U2 - 10.1016/j.kint.2020.05.051

DO - 10.1016/j.kint.2020.05.051

M3 - Journal articles

C2 - 32592813

AN - SCOPUS:85095805184

SN - 0085-2538

JO - Kidney International

JF - Kidney International

ER -