Enhanced control of BK polyomavirus in kidney transplant recipients is associated with distinct NK cell profiles 3693

Description BK polyomavirus (BKPyV) reactivation is associated with significant morbidity in kidney transplant recipients, who are at high-risk to develop BKPyV-associated nephropathy, one of the leading causes of graft loss. There is currently no effective treatment for BKPyV. Natural killer (NK) cell-based immunotherapy has the potential to treat BKPyV-associated diseases, yet NK cell response to BKPyV remains largely unexplored. Using NK cells from healthy donors, we first evaluated NK cell responses against BKPyV VP1 peptides by intracellular cytokine staining and detected robust CD107a upregulation and IFNy production by NK cells in about 35% of individuals. Next, we showed that NK cells efficiently limit BKPyV replication upon co-culture with BKPyV-infected renal tubular epithelial cells (RPTEC), with BKPyV production decreasing by 67% and lysis of RPTEC increasing up to 3-fold, as assessed by real-time qPCR and cytotoxicity assays. Finally, we examined NK cell profiles in 14 renal transplant recipients diagnosed with new onset of BKPyV DNAemia, including 5 who ultimately cleared the virus. Control of BKPyV was associated with NK cell subpopulations displaying less mature phenotypes, lower levels of PD-1, and higher expression of CXCR3 and IL-7 receptor. Collectively, these data suggest a role for NK cells in the control of BKPyV in vivo and indicate that NK cell responses may have the potential to be harnessed to enhance protection against BKPyV-associated diseases.