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Journal of Virology, March 2005, p. 2869-2879, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.2869-2879.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Identification of Cytomegalovirus-Specific Cytotoxic T Lymphocytes In Vitro Is Greatly Enhanced by the Use of Recombinant Virus Lacking the US2 to US11 Region or Modified Vaccinia Virus Ankara Expressing Individual Viral Genes

Naeem Khan,1 Rachel Bruton,1 Graham S. Taylor,1 Mark Cobbold,1 Thomas R. Jones,2 Alan B. Rickinson,1 and Paul A. H. Moss1*

CR UK Institute for Cancer Studies, Edgbaston, University of Birmingham, Birmingham, United Kingdom,1 Infectious Disease Section, Wyeth Research, Pearl River, New York2

Received 18 July 2004/ Accepted 18 October 2004

Cytomegalovirus (CMV) elicits a potent T-cell response in humans that appears to protect the host from virus-associated disease. Despite facing strong host defense mechanisms, CMV remains as a lifelong infection that may reactivate and cause life-threatening disease in immunocompromised individuals. This persistence is probably assisted by expression of immune subversion proteins of the virus encoded by genes belonging to the US gene family. These proteins modulate major histocompatibility complex expression in infected cells and bias in vitro experiments toward the detection of only certain specificities. We have combined the use of recombinant CMV, lacking the US2 to US11 region genes, and cytoplasmic gamma interferon staining to define a more accurate assessment of CMV-specific responses in vivo. Recombinant CMV stimulation reveals a CD8 response much larger than that of parental virus in all donors tested. In some cases, this represented up to 10-fold increases in the number of cells detected. Responses were directed mainly against pp65, IE-1, and pp50 in the majority of donors. In addition, previously unreported IE-2-specific T-cell responses could be detected in a minority of cases. Furthermore, we observed a less marked increase in the response to mutant CMV by CD4 T cells in some donors. This suggests that a much broader T-cell response to CMV exists in vivo than is revealed by restimulation with wild-type virus and adds to the evidence that the efficacy of immune evasion strategies may not be as absolute as previously believed.

* Corresponding author. Mailing address: CR UK Institute for Cancer Studies, Vincent Dr., Edgbaston, University of Birmingham, Birmingham B15 2TA, United Kingdom. Phone: 44 121 4142824. Fax: 44 121 4144486. E-mail: p.moss{at}bham.ac.uk.

Journal of Virology, March 2005, p. 2869-2879, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.2869-2879.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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