Characterization of the CD4+ T Cell Response to Epstein-Barr Virus during Primary and Persistent Infection

doi:10.1084/jem.20022058

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Published 15 September 2003. doi:10.1084/jem.20022058

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© Rockefeller University Press, 0022-1007/2003/9/903 $5.00
The Journal of Experimental Medicine, Volume 198, Number 6, 903-911

Characterization of the CD4⁺ T Cell Response to Epstein-Barr Virus during Primary and Persistent Infection

Elisabeth Amyes¹, Chris Hatton², Damien Montamat-Sicotte¹, Nancy Gudgeon³, Alan B. Rickinson³, Andrew J. McMichael¹ and Margaret F.C. Callan¹

¹ Medical Research Council (MRC) Human Immunology Unit, Weatherall Institute of Molecular Medicine
² Department of Haematology, The John Radcliffe, OX3 9DS Oxford, United Kingdom
³ Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, B15 2TT Birmingham, United Kingdom

Address correspondence to Margaret Callan, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, OX3 9DS Oxford, United Kingdom. Phone: 44-1865-222448; Fax: 44-1865-222502; email: mcallan{at}molbiol.ox.ac.uk

The CD8⁺ T cell response to Epstein-Barr virus (EBV) is wellcharacterized. Much less is known about the evolution of theCD4⁺ T cell response. Here we show that EBV stimulates a primaryburst of effector CD4⁺ T cells and this is followed by a periodof down-regulation. A small population of EBV-specific effectorCD4⁺ T cells survives during the lifelong persistent phase ofinfection. The EBV-specific effector CD4⁺ T cells accumulatewithin a CD27⁺ CD28⁺ differentiation compartment during primaryinfection and remain enriched within this compartment throughoutthe persistent phase of infection. Analysis of CD4⁺ T cell responsesto individual epitopes from EBV latent and lytic cycle proteinsconfirms the observation that the majority of the effector cellsexpress both CD27 and CD28, although CD4⁺ T cells specific forlytic cycle antigens have a greater tendency to express CD45RAthan those specific for the latent antigens. In clear contrast,effector CD4⁺ T cells specific for cytomegalovirus (CMV) accumulatewithin the CD27^- CD28⁺ and CD27^- CD28^- compartments. There arestriking parallels in terms of the differentiation of CD8⁺ Tcells specific for EBV and CMV. The results challenge currentideas on the definition of memory subsets.

Key Words: immunity • antigens CD27 • antigens CD28 • Epstein-Barr virus • cytomegalovirus

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