Flow cytometric quantitation and characterization of the T-lymphocyte memory response to CMV in healthy donors

Cytotherapy. 2002;4(1):29-40. doi: 10.1080/146532402317251509.


Background: Levels of circulating CMV Ag-specific lymphocytes determine CMV reactivation risk in immunocompromised individuals.

Methods: Frequencies of T cells producing cytokines after stimulation by CMV Ag were measured in hematopoietic stem-cell donors using flow cytometry.

Results: In seropositive individuals (n = 75) the mean number of CD8(+) (CD8(bright), CD8(dim)) and CD4(+) cells producing IFN-gamma was respectively 3.1% (12.6/microL) and 0.38% (3.2/microL), over 10-fold higher than in seronegative subjects (n = 22). CMV stimulation induced tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in both CD4(+) and CD8(+) cells (usually together), with a shift from memory- to effector-cell phenotype, while only a small proportion of CD4(+) cells produced IL-4. Although the normal range was wide, neither age, sex nor HLA type affected the frequency.

Discussion: These quantitative studies and the recognition of CD4(+) cells as potential effectors of CMV immunity are of relevance for immunotherapeutic approaches to prevent CMV disease after stem-cell transplantation.

MeSH terms

  • Adoptive Transfer / methods
  • Antigens, Viral / immunology
  • Cytomegalovirus / immunology*
  • Flow Cytometry / methods
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunologic Memory*
  • Interferon-gamma / biosynthesis
  • T-Lymphocyte Subsets / classification
  • T-Lymphocyte Subsets / immunology*
  • Tissue Donors*
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Antigens, Viral
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma