Dynamics of virus‐specific T cell immunity in pediatric liver transplant recipients

Immunosuppression following solid organ transplantation (SOT) has a deleterious effect on cellular immunity leading to frequent and prolonged viral infections. To better understand the relationship between posttransplant immunosuppression and circulating virus‐specific T cells, we prospectively monitored the frequency and function of T cells directed to a range of latent (CMV, EBV, HHV6, BK) and lytic (AdV) viruses in 16 children undergoing liver transplantation for up to 1 year posttransplant. Following transplant, there was an immediate decline in circulating virus‐specific T cells, which recovered posttransplant, coincident with the introduction and subsequent routine tapering of immunosuppression. Furthermore, 12 of 14 infections/reactivations that occurred posttransplant were successfully controlled with immunosuppression reduction (and/or antiviral use) and in all cases we detected a temporal increase in the circulating frequency of virus‐specific T cells directed against the infecting virus, which was absent in 2 cases where infections remained uncontrolled by the end of follow‐up. Our study illustrates the dynamic changes in virus‐specific T cells that occur in children following liver transplantation, driven both by active viral replication and modulation of immunosuppression. This prospective study follows a cohort of pediatric liver transplant recipients from pretransplant to 1 year posttransplant, sequentially monitoring cellular immunity to a range of latent and lytic viruses, demonstrating that dynamic changes in the frequency of virus‐specific T cells occur in response to immunosuppressive modulation and viral replication.