Submitted March 8, 2007
Accepted May 21, 2007
High T-cell response to human cytomegalovirus induces chemokine-mediated endothelial cell damage
Cynthia A Bolovan-Fritts, Rodney N Trout, and Stephen A Spector*
Department of Pediatrics, Division of Infectious Diseases, University of California San Diego, La Jolla, CA, United States
Center for Molecular Genetics, University of California, San Diego, La Jolla, CA, United States
* Corresponding author; email: saspector{at}ucsd.edu.
Human cytomegalovirus (CMV) infection has been linked to inflammatory diseases including vascular disease and chronic transplant rejection that involve vascular endothelial damage. We have previously reported that the host CD4+ T-cell response to CMV antigen presented by endothelial cells can produce IFN
and TNF
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, and MIP-1
together with cell adhesion markers in endothelial cells when compared to 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 leading 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 where a high antigen-specific T-cell response defines an important risk factor for development of chronic inflammation and endothelial cell injury.
