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Prepublished online as a Blood First Edition Paper on April 17, 2002; DOI 10.1182/blood-2002-01-0160.
Submitted January 18, 2002
Accepted March 22, 2002
Epstein Barr virus-specific CD8+ T cells that re-express CD45R apoptosis-resistant memory cells that retain replicative potential
Padraic J Dunne, Jeffery M Faint, Nancy H Gudgeon, Jean M Fletcher, Fiona J Plunkett, Maria V D Soares, Andrew D Hislop, Nicola E Annels, Alan B Rickinson, Mike Salmon, and Arne N Akbar*
Department of Clinical Immunology, Royal Free and University College Medical School, London, United Kingdom
Medical Research Council Centre for Immune Regulation, Birmingham University Medical School, Birmingham, United Kingdom
Cancer Research Campaign Institute for Cancer Studies, Birmingham University Medical School, Birmingham, United Kingdom
* Corresponding author; email: a.akbar{at}rfc.ucl.ac.uk.
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 not known. We now demonstrate that, relative to their CD45RO+ counterparts, the EBV-specific CD8+ T cells that revert to CD45RA expression after acute infectious mononucleosis (AIM) are not in cell cycle, have longer telomeres and are more resistant to apoptosis partly due to 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 peptide. 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 immuno-compromised and elderly individuals.
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