High T-cell response to human cytomegalovirus induces chemokine-mediated endothelial cell damage
Open Access
- 15 September 2007
- journal article
- Published by American Society of Hematology in Blood
- Vol. 110 (6), 1857-1863
- https://doi.org/10.1182/blood-2007-03-078881
Abstract
Human cytomegalovirus (CMV) infection has been linked to inflammatory diseases that involve vascular endothelial damage, including vascular disease and chronic transplant rejection. We previously reported that the host CD4+ T-cell response to CMV antigen presented by endothelial cells can produce interferon-γ and tumor necrosis factor-α at levels sufficient to drive induction of fractalkine, a key marker of inflammation, in endothelial cells. In this work, we report that donors with high frequencies of antigen-specific T cells to CMV (high responders) induce higher levels of activation-associated chemokines such as fractalkine, RANTES (regulated on activation, normal T cell expressed and secreted), and macrophage inflammatory protein-1β, together with cell-adhesion markers in endothelial cells compared with donors with low levels of CMV-specific T cells (low responders). High-responder cultures had higher levels of leukocyte recruitment and adherence to the endothelial monolayers associated with progressive damage and loss of the endothelial cells. These processes that led to endothelial destruction only required viral antigen and did not require infectious virus. Our findings further support that CMV may represent one member of a class of persistent pathogens in which a high antigen-specific T-cell response defines an important risk factor for development of chronic inflammation and endothelial cell injury.Keywords
This publication has 32 references indexed in Scilit:
- CD8 T Cells Control Cytomegalovirus Latency by Epitope-Specific Sensing of Transcriptional ReactivationJournal of Virology, 2006
- Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjectsThe Journal of Experimental Medicine, 2005
- The Safety of Discontinuation of Maintenance Therapy for Cytomegalovirus (CMV) Retinitis and Incidence of Immune Recovery Uveitis Following Potent Antiretroviral TherapyHIV Research & Clinical Practice, 2005
- Inflammation, Atherosclerosis, and Coronary Artery DiseaseNew England Journal of Medicine, 2005
- Human Cytomegalovirus-Specific CD4 + -T-Cell Cytokine Response Induces Fractalkine in Endothelial CellsJournal of Virology, 2004
- T cell response against the cytomegalovirus proteins pp65 and IE1Human Immunology, 2003
- Innate Immune RecognitionAnnual Review of Immunology, 2002
- Immune Mechanisms in AtherosclerosisArteriosclerosis, Thrombosis, and Vascular Biology, 2001
- Association between Prior Cytomegalovirus Infection and the Risk of Restenosis after Coronary AtherectomyNew England Journal of Medicine, 1996
- Enhancement of transplantation-associated atherosclerosis by CMV, which can be prevented by antiviral therapy in the form of HPMPCTransplant International, 1994