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| Item Type: | Article |
|---|---|
| Title: | Cytokine-mediated activation of kidney-infiltrating CD8(+) T cells enables their contribution to inflammation in human lupus nephritis |
| Creators: |
Skopnik, Christopher M., Klocke, Jan, Freund, Paul, Metzke, Diana, Ostendorf, Lennard, Bunse, Mario  ORCID: https://orcid.org/0000-0002-7554-2520, Prskalo, Luka, Kotzbauer, Johanna, Hinze, Christian ORCID: https://orcid.org/0000-0003-2526-1621, Grothgar, Emil, Goerlich, Nina, Wagner, Leonie, Daniel, Christoph, Hartmann, Arndt, Schneider, Udo, Biesen, Robert, Alexander, Tobias, Hauser, Anja E., Radbruch, Andreas, Eckardt, Kai-Uwe, Hiepe, Falk, Kruglov, Andrey, Mashreghi, Mir-Farzin and Enghard, Philipp
|
| Abstract: | Proliferative lupus nephritis (LN) is triggered by deposition of autoantibodies in glomeruli and paralleled by a T cell–rich kidney infiltrate. Although these T cells have been attributed to the propagation of tissue injury, it is unclear how they are activated and whether T cell autoreactivity drives local inflammation. Kidney-infiltrating T cells are also observed in urine, where they have high resemblance to interstitial T cells. Therefore, urinary T cells are a proxy for investigating tissue pathogenesis. Here, we analyzed urinary T cells to elucidate whether a kidney-specific T cell autoimmune reaction contributes to tubulointerstitial inflammation in LN. Using single-cell RNA sequencing, we compared transcriptomes and clonotypes of T cells from the blood and urine of patients with active LN and showed that urinary T cells were mostly activated CD8 effector memory cells recruited from a circulating CX3CR1(+) subset. Several urinary CD8 T cell clones were expanded. However, upon in vitro testing of their T cell receptors, we did not observe autoreactivity against autologous tubular epithelial cells. Instead, ~20% of expanded clonotypes were Epstein-Barr virus–specific or cytomegalovirus-specific, but respective viral antigens were undetectable in kidney biopsies or urine. Conversely, kidney-infiltrating T cells had access to interleukin-15 and interferon-β (IFN-β), and stimulation with these cytokines was sufficient to trigger degranulation and production of tumor necrosis factor, IFN-γ, and granzyme K. Together, these results show that CD8(+)CX3CR1(+) T cells are recruited into the kidney in LN, where they are activated by cytokines, enabling them to contribute to local inflammation. |
| Keywords: | CD8-Positive T-Lymphocytes, Cytokines, Inflammation, Kidney, Lupus Nephritis, Lymphocyte Activation, Male |
| Source: | Science Translational Medicine |
| ISSN: | 1946-6234 |
| Publisher: | American Association for the Advancement of Science |
| Volume: | 18 |
| Number: | 857 |
| Page Range: | eadz2015 |
| Date: | 8 July 2026 |
| Official Publication: | https://doi.org/10.1126/scitranslmed.adz2015 |
| PubMed: | View item in PubMed |
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