The 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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We thank M. Lucas for help; J. Collier and R. Chapman for blood samples from the Oxford clinic; T. Rostron for HLA typing; B. Walker, G. Lauer, E. Barnes and G. Dusheiko for collaboration; and the staff and patients of the clinics that provided blood samples, particularly the Caldecot Centre at King's College Hospital, the VA Research Center for AIDS and HIV Infection and the UCSD Center for AIDS Research. This work was supported by the Medical Research Council of the UK, the Wellcome Trust, the EU (QLK2-CT-1999-00356), Elizabeth Glaser Pediatric AIDS Foundation and the NIH. S.L.R.-J. is an MRC Senior Fellow and holds an Elizabeth Glaser scientist award.

Author information


  1. MRC Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK

    • Victor Appay
    • , P. Rod Dunbar
    • , Margaret Callan
    • , Geraldine M.A. Gillespie
    • , Laura Papagno
    • , Graham S. Ogg
    • , Abigail King
    • , Mariolina Salio
    • , Vincenzo Cerundolo
    • , Andrew J. McMichael
    •  & Sarah L. Rowland-Jones
  2. Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, Oxford, UK

    • Paul Klenerman
    •  & Franziska Lechner
  3. University of California San Diego, La Jolla, California, USA

    • Celsa A. Spina
    • , Susan Little
    • , Diane V. Havlir
    •  & Douglas D. Richman
  4. San Diego VA Research Center for AIDS and HIV Infection, San Diego, California, USA

    • Celsa A. Spina
    • , Susan Little
    •  & Douglas D. Richman
  5. Institute for Immunology, Munchen, Germany

    • Norbert Gruener
    •  & Gerd Pape
  6. Department of HIV/GUM, The Guy's, Kings' and St Thomas' School of Medicine, Weston Education Centre, London, UK

    • Anele Waters
    •  & Philippa Easterbrook


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Correspondence to Victor Appay.

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