Monitoring cytomegalovirus IE-1 and pp65-specific CD4+ and CD8+ T-cell responses after allogeneic stem cell transplantation may identify patients at risk for recurrent CMV reactivations

Cytometry B Clin Cytom. 2008 Jul;74(4):211-20. doi: 10.1002/cyto.b.20420.

Abstract

We studied the recovery of CMV-specific CD4+ and CD8+ T-cell immunity in 52 recipients of allogeneic stem cell transplantation (SCT). The proportions of IFN-gamma-producing CD4+ and CD8+ T cells upon in vitro activation using peptide pools representing the CMV pp65 and IE-1 proteins were assessed at multiple time points post SCT, and correlated with the occurrence of CMV reactivation. In a retrospective analysis, recurrent CMV reactivations occurred in 9 patients and were associated with low pp65-specific CD4+ T-cell and low IE-1-specific CD8(+) T-cell reactivities, whereas patients without detectable CMV reactivation (n = 30) or a single reactivation (n = 13) showed a better recovery of these immune responses. CD4+ T-cell responses to IE-1 were infrequent in most patients, whereas CD8+ T-cell responses to pp65 occurred frequently, but did not correlate with protection against (recurrent) reactivation. Prospectively, CMV-specific T-cell responses could be studied prior to 14 reactivation episodes in 8 patients. CD4+ T-cell responses to IE-1 and pp65 were positive in only 1 and 2 episodes, respectively. CD8+ T-cell responses against IE-1 were positive in 4, but against pp65 in 12 episodes, again showing that CD8+ T-cell reactivity against pp65 did not prevent CMV reactivation. Thus, monitoring of particular CMV-specific CD4+ and CD8+ T-cell responses after allogeneic SCT may identify patients at risk for recurrent CMV reactivations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus* / immunology
  • Cytomegalovirus* / physiology
  • Female
  • Humans
  • Immediate-Early Proteins / immunology*
  • Immunosuppression Therapy
  • Immunosuppressive Agents
  • Interferon-gamma / immunology
  • Male
  • Mice
  • Middle Aged
  • Phosphoproteins / immunology*
  • Recurrence
  • Retrospective Studies
  • Stem Cell Transplantation*
  • Transplantation, Homologous
  • Viral Matrix Proteins / immunology*
  • Virus Activation*
  • Virus Latency

Substances

  • IE1 protein, cytomegalovirus
  • Immediate-Early Proteins
  • Immunosuppressive Agents
  • Phosphoproteins
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa
  • Interferon-gamma