Functional patterns of cytomegalovirus (CMV) pp65 and immediate early-1-specific CD8(+) T cells that are associated with protection from and control of CMV DNAemia after allogeneic stem cell transplantation

Transpl Infect Dis. 2015 Jun;17(3):361-70. doi: 10.1111/tid.12391. Epub 2015 Jun 1.

Abstract

Background: The functional profile of cytomegalovirus (CMV)-specific CD8(+) T cells that associate with protection from and control of CMV DNAemia in allogeneic stem cell transplant (allo-SCT) recipients remains incompletely characterized.

Methods: We enumerated pp65 and immediate early (IE)-1-specific CD8(+) T cells expressing interferon-gamma, tumor necrosis factor-alpha, and CD107a, by flow cytometry in 94 patients at days +30 and +60 after allo-SCT.

Results: Fifty of 94 patients had CMV DNAemia within the first 100 days after transplant. CMV-specific CD8(+) T-cell responses (of any functional type) were more likely to be detected in patients who did not display CMV DNAemia than in those who did (P = 0.04). Qualitatively, no major differences in the functional signature of CMV-specific CD8(+) T cells were noted between patients who had or did not have CMV DNAemia. Patients displaying levels of polyfunctional CD8(+) T cells at day +30 >0.30 cell/μL had a lower risk of CMV DNAemia (positive predictive value 76%, and negative predictive value 43%).

Conclusion: The presence of polyfunctional CD8(+) T cells (either expressing CD107a or not) was associated with lower levels of CMV replication, and higher frequency of self-resolved episodes. The data reported further clarify the role of polyfunctional CD8(+) T cells in control of CMV DNAemia in allo-SCT recipients.

Keywords: CMV DNAemia; allogeneic stem cell transplant; cytomegalovirus; polyfunctional CD8+ T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cohort Studies
  • Cytomegalovirus / genetics
  • Cytomegalovirus / immunology*
  • Cytomegalovirus / metabolism
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / virology
  • DNA, Viral / blood*
  • Female
  • Humans
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Male
  • Middle Aged
  • Phosphoproteins / immunology
  • Phosphoproteins / metabolism*
  • Stem Cell Transplantation / adverse effects*
  • Transplantation, Homologous / adverse effects
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism
  • Viral Matrix Proteins / immunology
  • Viral Matrix Proteins / metabolism*
  • Young Adult

Substances

  • DNA, Viral
  • Phosphoproteins
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa
  • Interferon-gamma