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Prepublished online as a Blood First Edition Paper on April 17, 2002; DOI 10.1182/blood-2002-01-0160.
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Blood, 1 August 2002, Vol. 100, No. 3, pp. 933-940
IMMUNOBIOLOGY
Epstein-Barr virus-specific CD8+ T cells that
re-express CD45RA are apoptosis-resistant memory cells that retain
replicative potential
Padraic J. Dunne,
Jeffery
M. Faint,
Nancy H. Gudgeon,
Jean M. Fletcher,
Fiona J. Plunkett,
Maria Vieira D. Soares,
Andrew D. Hislop,
Nicola E. Annels,
Alan B. Rickinson,
Mike Salmon, and
Arne N. Akbar
From the Department of Clinical Immunology, Royal Free
and University College Medical School, London; the Cancer Research
Campaign Institute for Cancer Studies, Birmingham University Medical
School; and the Medical Research Council Centre for Immune Regulation,
Birmingham University Medical School, United Kingdom.
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
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
immunocompromised and elderly persons.
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