Reduced IL-7 responsiveness defined by signal transducer and activator of transcription 5 phosphorylation in T cells may be a marker for increased risk of developing cytomegalovirus disease in patients after hematopoietic stem cell transplantation

Biol Blood Marrow Transplant. 2014 Jan;20(1):128-32. doi: 10.1016/j.bbmt.2013.10.006. Epub 2013 Oct 15.

Abstract

Cytomegalovirus (CMV) reactivation may lead to CMV disease associated with high morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT); the identification of clinically relevant markers may aid in the identification of patients at increased risk for developing CMV-associated complications. We evaluated the phosphorylation of signal transducer and activator of transcription 5 (STAT5) in CD4(+) T cells, CD8(+) T cells, and TCRγδ T cells in response to stimulation with IL-7 or IL-2 after HSCT by analyzing blood samples taken monthly 1 to 6 months after HSCT. Patients were monitored weekly with a quantitative PCR from the time of engraftment for CMV viral load in whole blood until at least day 100 after HSCT. We identified a correlation between clinical outcome regarding CMV replication and the ability to respond to IL-7 and IL-2 defined by STAT5 phosphorylation (pSTAT5). Patients with recurrent or prolonged CMV replications had significantly lower pSTAT5 upon stimulation of T cells with either IL-7 or IL-2 at time points 1 through 3 than those without CMV replication (P < .05). This was also found after stimulation of CD8(+) T cells at time point 2 (P < .05). We conclude that reduced responses to IL-7, reflected by pSTAT5, may represent a clinically relevant functional biomarker for individuals at increased risk for CMV reactivation; our data may also aid in designing better strategies to improve anti-CMV immune responses without increasing the risk of developing graft-versus-host disease.

Keywords: Cytomegalovirus; Graft-versus-host disease; HSCT; Interleukin-2; Interleukin-7; Signal transducer and activator of transcription 5 (STAT5).

MeSH terms

  • Adult
  • Biomarkers / metabolism
  • Cells, Cultured
  • Cytomegalovirus / physiology*
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / pathology
  • Cytomegalovirus Infections / virology*
  • Female
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / pathology
  • Graft vs Host Disease / virology*
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / pathology
  • Hematologic Neoplasms / virology*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Interleukin-2 / pharmacology
  • Interleukin-7 / pharmacology
  • Male
  • Phosphorylation
  • Prospective Studies
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / immunology
  • STAT5 Transcription Factor / metabolism*
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / virology
  • Transplantation, Homologous
  • Viral Load
  • Virus Activation
  • Virus Replication

Substances

  • Biomarkers
  • IL7 protein, human
  • Interleukin-2
  • Interleukin-7
  • STAT5 Transcription Factor