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Blood, 1 January 2004, Vol. 103, No. 1, pp. 162-167.
Prepublished online as a Blood First Edition Paper on September 11, 2003; DOI 10.1182/blood-2003-06-1791.
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IMMUNOBIOLOGY
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,
Malcolm Rustin,
Wolfgang Bergler,
Peter C. L. Beverley,
Mike Salmon, and
Arne N. Akbar
From the Department of Immunology and Molecular Pathology, The Windeyer Institute for Medical Sciences, Royal Free and University College Medical School, London, United Kingdom; the Department of Histopathology, St James's University Hospital Leeds, United Kingdom; The CD45 Group, Edward Jenner Institute for Vaccine Research, Compton, Berkshire, United Kingdom; the Department of Rheumatology, MRC Center for Immune Regulation, University of Birmingham; the Department of Dermatology, Royal Free and University College Medical School, London, United Kingdom; and the Department of ORL, Head and Neck Surgery, University Hospital Mannheim, Theodor-Kutzer-Ufer, Mannheim, Germany;
Human-virus–specific CD8+ T cells that are found during primary infection have been studied almost exclusively in the peripheral blood, and it is unclear whether 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 the blood and tonsils of the same patients during acute infectious mononucleosis (AIM). Although the clonal composition of CD8+ T cells as determined by heteroduplex analysis was similar in both compartments, there was greater CD28 expression in the tonsil population, indicating that they were less differentiated. EBV-specific CD8+ T cells in both tissue types were extremely susceptible to apoptosis related to low Bcl-2 expression and were dependent on exogenous cytokines such as interleukin-2 (IL-2), IL-15, and interferon- / (IFN-/) for survival. In both compartments, however, these cells maintained their telomere lengths through telomerase induction. Thus, apoptosis-prone EBV-specific CD8+ T cells 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 found in blood and secondary lymphoid tissue.
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