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Journal of Virology, September 2000, p. 8140-8150, Vol. 74, No. 17
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Functional Heterogeneity and High Frequencies of Cytomegalovirus-Specific CD8+ T Lymphocytes in Healthy Seropositive Donors

Geraldine M. A. Gillespie,1,* Mark R. Wills,2 Victor Appay,1 Chris O'Callaghan,1 Mike Murphy,1 Neil Smith,3 Patrick Sissons,2 Sarah Rowland-Jones,1 John I. Bell,1 and Paul A. H. Moss4

MRC Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford,1 Department of Medicine, University of Cambridge Clinical School, Hills Road, Cambridge,2 National Blood Service, Oxford,3 and CRC Institute for Cancer Studies and MRC/Birmingham University Centre for Immune Regulation, Edgbaston, Birmingham,4 United Kingdom

Received 10 September 1999/Accepted 2 May 2000

Human cytomegalovirus (HCMV) infection is largely asymptomatic in the immunocompetent host, but remains a major cause of morbidity in immunosuppressed individuals. Using the recently described technique of staining antigen-specific CD8+ T cells with peptide-HLA tetrameric complexes, we have demonstrated high levels of antigen-specific cells specific for HCMV peptides and show that this may exceed 4% of CD8+ T cells in immunocompetent donors. Moreover, by staining with tetramers in combination with antibodies to cell surface markers and intracellular cytokines, we demonstrate functional heterogeneity of HCMV-specific populations. A substantial proportion of these are effector cytotoxic T lymphocytes, as demonstrated by their ability to lyse peptide-pulsed targets in "fresh" killing assays. These data suggest that the immune response to HCMV is periodically boosted by a low level of HCMV replication and that sustained immunological surveillance contributes to the maintenance of host-pathogen homeostasis. These observations should improve our understanding of the immunobiology of persistent viral infection.

* Corresponding author. Mailing address: MRC Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom. Phone: 44 1865 222312. Fax: 44 1865 222502. E-mail: ggillesp{at}molbiol.ox.ac.uk.

Journal of Virology, September 2000, p. 8140-8150, Vol. 74, No. 17
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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