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

Hum Immunol. 2004 May;65(5):486-92. doi: 10.1016/j.humimm.2004.02.020.

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.

MeSH terms

  • 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
  • Cytomegalovirus Infections / immunology*
  • 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
  • Virus Latency / immunology

Substances

  • Antigens, CD
  • CCR7 protein, human
  • CD11a Antigen
  • DNA, Viral
  • Immunoglobulin G
  • Immunoglobulin M
  • Immunosuppressive Agents
  • Interleukin-2
  • Ki-67 Antigen
  • Membrane Glycoproteins
  • Receptors, CCR7
  • Receptors, Chemokine
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Tumor Necrosis Factor-alpha
  • L-Selectin
  • Integrin alpha4
  • CD40 Ligand
  • Interleukin-4
  • Interferon-gamma
  • ADP-ribosyl Cyclase
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1
  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases