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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. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-06-1937v1 104/4/1075    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Manley, T. J. Articles by Riddell, S. R. Search for Related Content PubMed PubMed Citation Articles by Manley, T. J. Articles by Riddell, S. R. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY 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 From the Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA; and the Infectious Disease Section, Wyeth Research, Pearl River, NY. Although cytomegalovirus (CMV) expresses proteins that interfere with antigen presentation by class I major histocompatibility complex (MHC) molecules, CD8+ cytotoxic T cells (CTLs) 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 4 viral genes that are responsible for interfering with class I MHC presentation, was used to examine the frequency and specificity of the CD8+ CTLs 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+ CTLs 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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