Cytomegalovirus reactivation following allogeneic stem cell transplantation is associated with the presence of dysfunctional antigen-specific CD8+ T cells

Evren Özdemir, Lisa S. St John, Geraldine Gillespie, Sarah Rowland-Jones, Richard E. Champlin, Jeffrey J. Molldrem, Krishna V. Komanduri

Research output: Contribution to journalArticle

158 Scopus citations

Abstract

Cytomegalovirus (CMV) infection causes significant morbidity and mortality in the setting of immunodeficiency, including the immune reconstitution phase following allogeneic stem cell transplantation (SCT). We assessed CMV-specific CD4+ and CD8+ T-cell responses in 87 HLA-A*0201-positive (A2+) and/or B*0702-positive (B7+) allogeneic stem cell transplant recipients using HLA-peptide tetramer staining and cytokine flow cytometry (CFC) to examine the association of CMV-specific immune reconstitution and CMV antigenemia following SCT. Strong CMV-specific T-cell responses recovered in most subjects (77 of 87, 88%) after SCT. Frequencies of CMV-specific CD8+ T cells were significantly higher in those subjects who experienced early antigenemia relative to those who did not (2.2% vs 0.33%, P = .0002), as were frequencies of CMV-specific CD4+ T cells (1.71% vs 0.75%, P = .002). Frequencies of CMV-specific CD8+ T cells were also higher in subjects experiencing late antigenemia (2.4% vs 0.57%). When we combined tetramer staining and an assessment of cytokine production in a single assay, we found that individuals who experienced CMV antigenemia had lower tumor necrosis factor-α (TNF-α)-producing fractions of tetramer-staining CMV-specific CD8+ T cells than subjects who did not (25% vs 65%, P = .015). Furthermore, individuals at high risk for CMV reactivation, including patients with acute graft-versus-host disease and those receiving steroids, had low fractions of cytokine-producing CMV-specific CD8+ T cells (25% and 27%, respectively). These data suggest that the inability to control CMV reactivation following allogeneic SCT is due to the impaired function of antigen-specific CD8+ T cells rather than an inability to recover sufficient numbers of CMV-specific T cells.

Original languageEnglish (US)
Pages (from-to)3690-3697
Number of pages8
JournalBlood
Volume100
Issue number10
DOIs
StatePublished - Nov 15 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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