Correlations of programmed death 1 expression and serum IL-6 level with exhaustion of cytomegalovirus-specific T cells after allogeneic hematopoietic stem cell transplantation

Cell Immunol. 2014 Mar-Apr;288(1-2):53-9. doi: 10.1016/j.cellimm.2014.02.007. Epub 2014 Mar 11.

Abstract

The effect of programmed death 1 (PD-1) on cytomegalovirus (CMV)-specific T cells has not been thoroughly examined. We evaluated the involvement of exhausted CMV-specific T cells in persistent CMV infection after allogeneic hematopoietic stem cell transplantation (HSCT). CMV-specific CD8+ T cells obtained from an HLA-A∗24:02-positive patient, who failed to eliminate CMV for more than 1 year after HSCT, responded poorly to CMV pp65 peptide and showed high PD-1 expression. Sera from patients with persistent CMV infection showed a significantly higher IL-6 level than those from patients with temporary CMV infection after allogeneic HSCT and healthy donors. CD33+ adherent cells produced IL-6, and regulated PD-1 expression and growth of CMV-specific CD8+ T cells through cell-to-cell contact. Although further investigation is required to clarify the association between IL-6 level and CMV infection in more patients, IL-6 might be a useful biomarker of persistent CMV infection after allogeneic HSCT.

Keywords: Allogeneic hematopoietic stem cell transplantation; Cytomegalovirus-specific T cell; Exhaustion; IL-6; Programmed death 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Adhesion
  • Cell Communication
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / genetics*
  • Cytomegalovirus Infections / immunology
  • Cytomegalovirus Infections / pathology
  • Cytomegalovirus Infections / virology
  • Gene Expression
  • HLA-A24 Antigen / genetics
  • HLA-A24 Antigen / immunology
  • Hematopoietic Stem Cell Transplantation*
  • Host-Pathogen Interactions
  • Humans
  • Immune Tolerance
  • Interleukin-6 / genetics*
  • Interleukin-6 / immunology
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / genetics*
  • Programmed Cell Death 1 Receptor / immunology
  • Sialic Acid Binding Ig-like Lectin 3 / genetics
  • Sialic Acid Binding Ig-like Lectin 3 / immunology
  • Signal Transduction
  • Transplantation, Homologous
  • Viral Load

Substances

  • CD33 protein, human
  • HLA-A*24:02 antigen
  • HLA-A24 Antigen
  • IL6 protein, human
  • Interleukin-6
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Sialic Acid Binding Ig-like Lectin 3