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

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.