Nature Medicine
8, 379 - 385 (2002)
doi:10.1038/nm0402-379
Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infectionsVictor Appay1, P. Rod Dunbar1, Margaret Callan1, Paul Klenerman2, Geraldine M.A. Gillespie1, Laura Papagno1, Graham S. Ogg1, Abigail King1, Franziska Lechner2, Celsa A. Spina3, 4, Susan Little3, 4, Diane V. Havlir3, Douglas D. Richman3, 4, Norbert Gruener5, Gerd Pape5, Anele Waters6, Philippa Easterbrook6, Mariolina Salio1, Vincenzo Cerundolo1, Andrew J. McMichael1
& Sarah L. Rowland-Jones11
MRC Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK
2
Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, Oxford, UK
3
University of California San Diego, La Jolla, California, USA
4
San Diego VA Research Center for AIDS and HIV Infection, San Diego, California, USA
5
Institute for Immunology, Munchen, Germany
6
Department of HIV/GUM, The Guy's, Kings' and St Thomas' School of Medicine, Weston Education Centre, London, UK
Correspondence should be addressed to Victor Appay vappay@gwmail.jr2.ox.ac.ukThe viruses HIV-1, Epstein−Barr virus (EBV), cytomegalovirus (CMV) and hepatitis C virus (HCV) are characterized by the establishment of lifelong infection in the human host, where their replication is thought to be tightly controlled by virus-specific CD8+ T cells. Here we present detailed studies of the differentiation phenotype of these cells, which can be separated into three distinct subsets based on expression of the costimulatory receptors CD28 and CD27. Whereas CD8+ T cells specific for HIV, EBV and HCV exhibit similar characteristics during primary infection, there are significant enrichments at different stages of cellular differentiation in the chronic phase of persistent infection according to the viral specificity, which suggests that distinct memory T-cell populations are established in different virus infections. These findings challenge the current definitions of memory and effector subsets in humans, and suggest that ascribing effector and memory functions to subsets with different differentiation phenotypes is no longer appropriate.
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