NIV Congres

Introduction 70-100% of healthy individuals are latently infected with BKV. In renal transplant recipients (RTR) treated with immunosuppressive drugs, BKV systemically reactivates in ~30%, as defined by positive plasma PCR. In ~5% of these RTRs, BKV causes interstitial nephritis of the allograft, responsible for increased graft loss. CD8+ CTLs are essential in the defence against viruses. So far, peripherally circulating human BKV-specific CD8+ CTLs in healthy individuals have not been phenotypically characterized, due to their low frequencies in the circulation.

Methods and Results We used four different HLA-A02-tetramers (2 VP1 and 2 large T antigen epitopes) and applied steps that lower the detection limit: an extended incubation period with tetramers, and the measurement of large numbers of lymphocytes by flowcytometry. Therewith, we could show that BKV-specific CTLs were detectable directly ex vivo in 5 of 20 buffy coats from healthy HLA-A02-positive individuals, and are mainly VP1-specific. Phenotypic analysis showed that they are CD27int/hi CD28int/hi CD45RAint/lo CD127hi KLRG1int/lo and CCR7lo. Furthermore, they were CXCR3hi CD49dhi and CD38lo HLA-DRlo PD-1int/lo Ki67lo. Lastly, they were granzyme Kint, granzyme Blo and perforinlo, and T-betint and Eomesoderminlo/int.

Conclusion Peripherally circulating HLA-A02-restricted BKV-specific CD8+ CTLs in healthy individuals can be considered as KLRG1int/lo non-activated ‘effector memory’ T-cells that express some granzyme K, but no other cytotoxic effector molecules. These cells are important in suppressing BKV infection in healthy individuals. As such, it will be interesting to see how they differ from CD8+ CTLs in RTRs suffering from BKV pathology.