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

Am J Transplant. 2018 Sep;18(9):2238-2249. doi: 10.1111/ajt.14967. Epub 2018 Jul 10.

Abstract

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.

Keywords: T cell biology; clinical research/practice; infectious disease; liver transplantation/hepatology; monitoring: immune.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Graft Rejection / etiology*
  • Graft Rejection / pathology
  • Graft Survival / immunology*
  • Humans
  • Immunity, Cellular / immunology*
  • Immunosuppression Therapy
  • Immunosuppressive Agents / therapeutic use
  • Infant
  • Liver Transplantation / adverse effects*
  • Male
  • Postoperative Complications
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • T-Lymphocytes / immunology*
  • Transplant Recipients
  • Viral Load
  • Virus Diseases / immunology*
  • Virus Diseases / virology
  • Virus Replication
  • Viruses / immunology*
  • Young Adult

Substances

  • Immunosuppressive Agents