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Prepublished online as a Blood First Edition Paper on September 11, 2003; DOI 10.1182/blood-2003-06-1791.

Submitted June 4, 2003
Accepted August 27, 2003
The integration of apoptosis and telomere erosion in virus-specific CD8+ T cells from blood and tonsils during primary infection
Maria Vieira D Soares, Fiona J Plunkett, Caroline S Verbeke, Joanne E Cook, Jeff M Faint, Lavina L Belaramani, Jean M Fletcher, Nicholas Hammerschmitt, Malcom Rustin, Wolfgang Bergler, Peter C L Beverley, Mike Salmon, and Arne N Akbar*
Department of Immunology and Molecular Pathology, The Windeyer Institute for Medical Sciences, Royal Free and University College Medical School, London, United Kingdom
Department of Histopathology, St James's University Hospital Leeds, Leeds, United Kingdom
CD45 Group, Edward Jenner Institute for Vaccine Research, Compton, Berkshire, United Kingdom
Department of Rheumatology, MRC Center for Immune Regulation, University of Birmingham, Birmingham, United Kingdom
Department of ORL, Head and Neck Surgery, University Hospital Mannheim, Mannheim, Germany
Department of Dermatology, Royal Free and University College Medical School, London, United Kingdom
* Corresponding author; email: a.akbar{at}ucl.ac.uk.
Human virus-specific CD8+ T cells that are found during primary infection have been studied almost exclusively in the peripheral blood and it is not clear if these cells are regulated in the same way as those in secondary lymphoid tissue. We investigated therefore, the control of apoptosis and telomere erosion of Epstein-Barr Virus (EBV)-specific CD8+ T cells found in blood and tonsil of the same patients during acute infectious mononucleosis (AIM). Although the clonal composition of CD8+ T cells as determined by heteroduplex analysis was very similar in both compartments, there was greater CD28 expression on the tonsil population indicating that they were less differentiated. EBV-specific CD8+ T cells in both tissues were extremely susceptible to apoptosis related to low Bcl-2 expression and were dependent on exogenous cytokines such as IL-2, IL-15 and IFN- / for survival. However, these cells in both compartments maintain their telomere length through telomerase induction. Thus, apoptosis-prone EBV-specific CD8+ T cells that are found during acute infection have to be rescued from death to persist as a memory population. However, signals that induce telomerase ensure that the rescued cells retain their replicative capacity. Significantly, these processes operate identically in cells that are found in blood and secondary lymphoid tissue.

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