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. 2025 Jun 4.
doi: 10.1007/s40620-025-02298-2. Online ahead of print.

Urine-derived renal tubular epithelial cells resemble functional characteristics of professional antigen-presenting cells and can directly induce BKV-specific T cell responses

Toralf Roch #  1   2   3 , Krystallenia Paniskaki #  1   4 , Patrizia Wehler  1   2 , Constantin J Thieme  2   3 , Hanieh Moradian  5 , Arturo Blazquez-Navarro  1   2 , Moritz Anft  1 , Petra Reinke  3 , Timm H Westhoff  1 , Ulrik Stervbo  1   2 , Nina Babel  6   7   8
Affiliations

Urine-derived renal tubular epithelial cells resemble functional characteristics of professional antigen-presenting cells and can directly induce BKV-specific T cell responses

Toralf Roch et al. J Nephrol. .

Abstract

Background: Reactivation of the BK virus (BKV) is a critical adverse event after kidney transplantation and can lead to graft loss. BKV-reactive T cell-mediated viral control can be facilitated by reducing immunosuppression. However, the exact mechanism underlying the T cell-mediated BKV clearance in the kidney transplant is not clear.

Methods: Here, we used urine-derived renal tubular epithelial cells as a model system to investigate the immunomodulatory capacity of urine-derived renal tubular epithelial cells and their potential to induce T cell responses against BKV. Urine-derived renal tubular epithelial cells were generated by culturing urine-derived cell pellets. To assess the inflammatory potential of urine-derived renal tubular epithelial cells, the cells were treated with Poly I:C or TNFα/IFNγ. To investigate urine-derived renal tubular epithelial cell-induced T cell responses, autologous T cells, isolated from blood were co-cultured with urine-derived renal tubular epithelial cells, in the presence of BKV protein-derived peptides and PolyI:C or TNFα/IFNγ. BKV-reactive T cells, cytokine/chemokine secretion and expression of co-stimulatory molecules were evaluated using multiplex assays and multi-parameter flow cytometry.

Results: Urine-derived renal tubular epithelial cells phenotypically resemble renal tubular epithelial cells, as they express CD13, EPCAM, cytokeratin and the myo-inositol oxygenase. After stimulation with PolyI:C, urine-derived renal tubular epithelial cells showed increased levels of CD40 and HLA-ABC, whereas TNFα/IFNγ only induced HLA-DR/ABC expression. Poly I:C and TNFα/IFNγ stimulation of urine-derived renal tubular epithelial cells induced a district pattern of inflammatory cytokines and chemokines that facilitate the migration of certain immune cell subsets. Interestingly, urine-derived renal tubular epithelial cells can present BKV peptides, thereby inducing a functional BKV-reactive CD4 and CD8 T cell response.

Conclusions: Urine-derived renal tubular epithelial cells express immunomodulatory molecules, and induce BKV-directed T cell reactivity, indicating that renal epithelial cells may serve as non-conventional antigen-presenting cells in the kidney and thereby help BKV clearance.

Keywords: BKV; Renal transplantation; Specific T cells; UdTEC; Urine derived renal tubular epithelial cell.

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Conflict of interest statement

Declarations. Conflict of interest: Nothing to disclose. Ethical approval: The study was approved by the Ethics Committee of the Charité – Universitätsmedizin Berlin (EA4/276/21). Human and Animal Rights: All procedures followed have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Informed consent to participate: Written informed consent was obtained from all participants.

References

    1. Bussalino E, Marsano L, Parodi A et al (2021) Everolimus for BKV nephropathy in kidney transplant recipients: a prospective, controlled study. J Nephrol 34(2):531–538. https://doi.org/10.1007/s40620-020-00777-2 - DOI - PubMed
    1. Babel N, Volk HD, Reinke P (2011) BK polyomavirus infection and nephropathy: the virus–immune system interplay. Nat Rev Nephrol 7(7):399–406. https://doi.org/10.1038/nrneph.2011.59 - DOI - PubMed
    1. Schachtner T, Stein M, Sefrin A et al (2014) Inflammatory activation and recovering BKV-specific immunity correlate with self-limited BKV replication after renal transplantation. Transpl Int 27(3):290–301. https://doi.org/10.1111/tri.12251 . (Epub 2013 Dec 17) - DOI - PubMed
    1. Parajuli S, Jorgenson M, Meyers RO et al (2021) Role of virus-specific T cell therapy for cytomegalovirus and BK infections in kidney transplant recipients. Kidney 360. 2(5):905–915. https://doi.org/10.34067/KID.0001572021 - DOI - PubMed - PMC
    1. Stervbo U, Nienen M, Weist BJD et al (2019) BKV clearance time correlates with exhaustion state and T-cell receptor repertoire shape of BKV-specific T-cells in renal transplant patients. Front Immunol 10:767. https://doi.org/10.3389/fimmu.2019.00767 - DOI - PubMed - PMC

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