Functional specific-T-cell expansion after first cytomegalovirus reactivation predicts viremia control in allogeneic hematopoietic stem cell transplant recipients

Transpl Infect Dis. 2017 Dec;19(6). doi: 10.1111/tid.12778. Epub 2017 Oct 25.

Abstract

The use of preemptive antiviral therapy to prevent cytomegalovirus (CMV) disease in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients might result in over-treatment, inducing drug-related toxicity and viral resistance. A search for predictive markers is needed to determine requirement for antiviral therapy. Clinical follow-up, in combination with the use of streptamers (STs) and cytokine-intracellular staining, could help to identify patients at high risk for CMV reactivations. To study the immune response and reactivation control by CMV-specific CD8+ T-cell (CMV-CTL) populations, we monitored 25 patients who have undergone allo-HSCT by using ST multimer and intracellular cytokine staining. Our study has revealed that the presence of functional CMV-specific T cells, determined by early interferon γ production or by significant T-cell expansion after first CMV reactivation, correlated with short CMV viremia duration and low number of CMV reactivations. By contrast, the absence of functional CMV-CTLs does correlate with CMV recurrence. These results support that behavior of CMV-specific subpopulations after reactivation influences reactivations and can guide preemptive therapy.

Keywords: CD8+ T cells; bone marrow; cellular immunology; immune responses; transplantation.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Antibiotic Prophylaxis / adverse effects*
  • Antibiotic Prophylaxis / methods
  • Antiviral Agents / adverse effects
  • Biomarkers / blood
  • CD8-Positive T-Lymphocytes / virology*
  • Cytomegalovirus / drug effects
  • Cytomegalovirus / isolation & purification
  • Cytomegalovirus / physiology
  • Cytomegalovirus Infections / blood*
  • Cytomegalovirus Infections / diagnosis
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / prevention & control
  • Drug Resistance, Viral / drug effects
  • Female
  • Follow-Up Studies
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Immunity, Cellular
  • Male
  • Middle Aged
  • Patient Selection
  • Transplant Recipients
  • Transplantation, Homologous / adverse effects
  • Viremia / prevention & control
  • Virus Activation*

Substances

  • Antiviral Agents
  • Biomarkers