Epstein-Barr virus-specific CD8(+) T cells that re-express CD45RA are apoptosis-resistant memory cells that retain replicative potential

PJ Dunne, Jeffrey Faint, Nancy Gudgeon, J Fletcher, FJ Plunkett, MVD Scares, Andrew Hislop, NE Annels, Alan Rickinson, Michael Salmon, Ali Akbar

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

During acute infection, latent and lytic Epstein-Barr virus (EBV) epitope-specific CD8(+) T cells have a CD45RO(+) CD45RA(-)-phenotype. However, after resolution of the infection, a large proportion of these cells, particularly those specific for lytic viral epitopes, re-express the CD45RA molecule. The role of CD8(+) CD45RA(+) T cells in ongoing immunity to EBV and other viruses is unknown. We now demonstrate that, relative to their CD45RO(+) counterparts, the EBV-specific CD8(+) T cells that revert to CD45RA expression after acute infectious mononucleosis are not in cell cycle, have longer telomeres, and are more resistant to apoptosis partly because of increased Bcl-2 expression. However, the EBV-specific CD8(+) CD45RA(+) T cells have shorter telomeres than the total CD8(+) CD45RA(+) T-cell pool and predominantly express low levels of the CCR7 chemokine receptor, indicating that they are not naive cells. In addition, EBV-specific CD8(+) CD45RA(+) T cells can be induced to proliferate and exhibit potent cytotoxic activity against target cells loaded with specific pep-tide. Our results strongly suggest, therefore, that EBV-specific CD8(+) CD45RA(+) T cells represent a stabilized virus-specific memory pool and not terminally differentiated effector cells. The identification of mechanisms that enable stable virus-specific CD8(+) T cells to persist after acute infection may lead to the enhancement of antiviral immunity in immunocompromised and elderly persons.
Original languageEnglish
Pages (from-to)933-940
Number of pages8
JournalBlood
Volume100
Issue number3
Early online date17 Apr 2002
DOIs
Publication statusPublished - 1 Aug 2002

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