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.

• Authors: 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
• Journal: Kidney international (Kidney Int) Vol. 99 Issue 1 Pg. 238-246 (01 2021) ISSN: 1523-1755 [Electronic] United States
• PMID: 32592813 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antigens, Nuclear
• Cytokines

Topics

• Antigens, Nuclear
• CD4-Positive T-Lymphocytes
• Cytokines
• Humans
• Kidney
• Lupus Erythematosus, Systemic