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Blood, 15 August 2004, Vol. 104, No. 4, pp. 1075-1082.
Prepublished online as a Blood First Edition Paper on March 23, 2004; DOI 10.1182/blood-2003-06-1937.
Previous Article | Next Article 
Submitted June 16, 2003
Accepted March 10, 2004
Immune Evasion Proteins of Human Cytomegalovirus Do Not Prevent A Diverse CD8+ Cytotoxic T Cell Response In Natural Infection
Thomas J Manley*, Lisa Luy, Thomas Jones, Michael Boeckh, Helen Mutimer, and Stanley R Riddell
Program In Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; University of Washington, Seattle, WA, USA
Program In Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Infectious Disease Section, Wyeth Research, Pearl River, NY, USA
Program in Infectious Disease, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; University of Washington, Seattle, WA, USA
* Corresponding author; email: tmanley{at}fhcrc.org.
Although cytomegalovirus (CMV) expresses proteins that interfere with antigen presentation by class I MHC molecules, CD8+ cytotoxic T cells (CTL) are indispensable for controlling infection and maintaining latency. Here, a cytokine flow cytometry assay that employs fibroblasts infected with a mutant strain of CMV (RV798), which is deleted of the four viral genes that are responsible for interfering with class I MHC presentation, was used to examine the frequency and specificity of the CD8+ CTL to CMV in immunocompetent CMV seropositive individuals. A large fraction of the CD8+ CTL response was found to be specific for viral antigens expressed during the immediate early and early phases of virus replication and presented by fibroblasts infected with RV798 but not wild type CMV. These results demonstrate that the inhibition of class I antigen presentation observed in CMV-infected cells in vitro is not sufficient to prevent the induction of a broad repertoire of CD8+ CTL after natural infection in vivo. Thus, reconstitution of T-cell immunity in immunodeficient patients by cell therapy or by vaccination may need to target multiple viral antigens to completely restore immunologic control of CMV.

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