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Journal of Virology, December 2004, p. 13173-13181, Vol. 78, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.23.13173-13181.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Human Cytomegalovirus-Specific CD4⁺-T-Cell Cytokine Response Induces Fractalkine in Endothelial Cells

Cynthia A. Bolovan-Fritts,¹ Rodney N. Trout,¹ and Stephen A. Spector^1,2,3*

Department of Pediatrics, Division of Infectious Diseases,¹ Center for Molecular Genetics,² Center for AIDS Research, University of California San Diego, La Jolla, California³

Received 28 May 2004/ Accepted 8 July 2004

Cytomegalovirus (CMV) infection has been linked to inflammation-related disease processes in the human host, including vascular diseases and chronic transplant rejection. The mechanisms through which CMV affects the pathogenesis of these diseases are for the most part unknown. To study the contributing role of the host immune response to CMV in these chronic inflammatory processes, we examined endothelial cell interactions with peripheral blood mononuclear cells (PBMC). Endothelial cultures were monitored for levels of fractalkine induction as a marker for initiating the host inflammatory response. Our results demonstrate that in the presence of CMV antigen PBMC from normal healthy CMV-seropositive donors produce soluble factors that induce fractalkine in endothelial cells. This was not observed in parallel assays with PBMC from seronegative donors. Examination of subset populations within the PBMC further revealed that CMV antigen-stimulated CD4⁺ T cells were the source of the factors, gamma interferon and tumor necrosis factor alpha, driving fractalkine induction. Direct contact between CD4⁺ cells and the endothelial monolayers is required for this fractalkine induction, where the endothelial cells appear to provide antigen presentation functions. These findings indicate that CMV may represent one member of a class of persistent pathogens where the antigen-specific T-cell response can result in the induction of fractalkine, leading to chronic inflammation and endothelial cell injury.

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* Corresponding author. Mailing address: Department of Pediatrics, University of California at San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0672. Phone: (858) 534-7055. Fax: (858) 534-7411. E-mail: saspector{at}ucsd.edu.

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Journal of Virology, December 2004, p. 13173-13181, Vol. 78, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.23.13173-13181.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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