Properties of CD4(+) T cells in human cytomegalovirus infection

Laila E Gamadia*, Rob J Rentenaar, René A W van Lier, Ineke J M ten Berge

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The correlates of protective immunity to disease-inducing viruses in man remain to be elucidated. We determined the kinetics and properties of cytomegalovirus (CMV)-specific CD4(+) T cells in healthy individuals and renal transplant recipients during different stages of CMV infection. Our data reveal that circulating CMV-specific CD4(+) T cells displayed an effector-memory phenotype, and produced the T helper 1 cytokines interferon-gamma and tumor necrosis factor-alpha. In addition, they lacked molecules for secondary lymphoid organ homing and expressed the cytotoxic molecule granzyme B, inferring a direct role of these cells at target sites of infection. In asymptomatic individuals the CMV-specific CD4(+) T-cell response preceded CMV-specific CD8(+) T-cell responses, whereas in symptomatic individuals the CMV-specific effector memory CD4(+) T-cell response was delayed and only detectable after antiviral therapy. The appearance of disease symptoms in these patients suggests that functional CD8(+) T cell and antibody responses are insufficient to control viral replication and that formation of effector memory CD4(+) T cells is necessary for recovery of infection.

Original languageEnglish
Pages (from-to)486-492
Number of pages7
JournalHuman Immunology
Volume65
Issue number5
DOIs
Publication statusPublished - May 2004
Externally publishedYes

Keywords

  • ADP-ribosyl Cyclase/metabolism
  • ADP-ribosyl Cyclase 1
  • Antigens, CD/metabolism
  • CD11a Antigen/metabolism
  • CD4-Positive T-Lymphocytes/immunology
  • CD40 Ligand/metabolism
  • CD8-Positive T-Lymphocytes/immunology
  • Cross-Sectional Studies
  • Cytomegalovirus Infections/etiology
  • DNA, Viral
  • Flow Cytometry
  • Granzymes
  • Humans
  • Immunoglobulin G/blood
  • Immunoglobulin M/blood
  • Immunosuppressive Agents/pharmacology
  • Integrin alpha4/metabolism
  • Interferon-gamma/metabolism
  • Interleukin-2/metabolism
  • Interleukin-4/metabolism
  • Ki-67 Antigen/metabolism
  • Kidney Transplantation/adverse effects
  • L-Selectin/metabolism
  • Longitudinal Studies
  • Membrane Glycoproteins
  • Receptors, CCR7
  • Receptors, Chemokine/metabolism
  • Serine Endopeptidases/metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 7/metabolism
  • Tumor Necrosis Factor-alpha/metabolism
  • Viral Load
  • Virus Latency/drug effects

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