Differentiation of cytomegalovirus-specific CD8(+) T cells in healthy and immunosuppressed virus carriers

Blood. 2001 Aug 1;98(3):754-61. doi: 10.1182/blood.v98.3.754.


During immunosuppression, cytomegalovirus (CMV) can reactivate and cause serious clinical problems. Normally, abundant virus replication is suppressed by immune effector mechanisms. To study the interaction between CD8(+) T cells and persisting viruses, frequencies and phenotypes of CMV-specific CD8(+) T cells were determined in healthy individuals and compared to those in renal transplant recipients. In healthy donors, function of circulating virus-specific CD8(+) T cells, as measured by peptide-induced interferon gamma (IFN-gamma) production, but not the number of virus-specific T cells enumerated by binding of specific tetrameric peptide/HLA complexes, correlated with the number of CMV-specific IFN-gamma-secreting CD4(+) helper T cells. Circulating CMV- specific CD8(+) T cells did not express CCR7 and may therefore not be able to recirculate through peripheral lymph nodes. Based on coexpression of CD27 and CD45R0 most CMV-specific T cells in healthy donors appeared to be memory-type cells. Remarkably, frequencies of CMV-specific CD8(+) T cells were significantly higher in immunosuppressed individuals than in healthy donors. In these patients CMV-specific cells predominantly had an effector phenotype, that is, CD45R0(+)CD27(-)CCR7(-) or CD45RA(+)CD27(-)CCR7(-) and contained both granzyme B and perforin. Our data show that in response to immunosuppressive medication quantitative and qualitative changes occur in the CD8(+) T-cell compartment. These adaptations may be instrumental to maintain CMV latency. (Blood. 2001;98:754-761)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology*
  • Case-Control Studies
  • Cell Differentiation / immunology*
  • Cytomegalovirus / growth & development
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / blood
  • Cytomegalovirus Infections / immunology
  • Granzymes
  • HLA Antigens / metabolism
  • Humans
  • Immunocompromised Host / immunology*
  • Immunophenotyping
  • Kidney Transplantation / immunology
  • Longitudinal Studies
  • Receptors, Immunologic / metabolism
  • Receptors, KIR
  • Serine Endopeptidases / metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
  • Virus Activation


  • HLA Antigens
  • Receptors, Immunologic
  • Receptors, KIR
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases