Dendritic Cells Pulsed with Polyomavirus BK Antigen Induce Ex Vivo Polyoma BK Virus–Specific Cytotoxic T-Cell Lines in Seropositive Healthy Individuals and Renal Transplant Recipients

Abstract

Polyoma BK virus (BKV)-associated interstitial nephritis has emerged as a relevant complication of immunocompromise after kidney transplantation, leading to reduced survival of the renal allograft. The limitations of current antiviral treatment and the high probability of rejection in kidney graft recipients when control of viral replication is attempted by reduction of immunosuppression warrant further efforts to develop alternative therapeutic tools. Cellular immunotherapy has proved to be a successful approach for prevention and/or treatment of other viral complications in the immunocompromised host. For assessing the feasibility of translating this strategy to the prevention of BKV-associated disease, a procedure for ex vivo reactivation of BKV-specific cytotoxic T cells (CTL) was developed from BKV-seropositive healthy donors and allograft recipients through stimulation with dendritic cells pulsed with inactivated BKV. The CTL lines thus obtained showed BKV specificity, as an efficient lysis of BKV-infected targets was accompanied by little or no reactivity against mock-infected autologous or allogeneic targets. In vitro killing of allogeneic BKV-infected targets, likely as a result of populations of TCRgammadelta+/CD3+ displaying MHC class I unrestricted cytotoxicity, was also displayed. Application of this culture system may allow a preemptive therapy approach to BKV-related complications in transplant recipients, based on CTL treatment guided by BKV DNA levels.