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 language | English |
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Pages (from-to) | 486-492 |
Number of pages | 7 |
Journal | Human Immunology |
Volume | 65 |
Issue number | 5 |
DOIs | |
Publication status | Published - May 2004 |
Externally published | Yes |
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