1. ¹ Peter Medawar Building for Pathogen Research, Nuffield Department Of Medicine, University of Oxford, South Parks Road, Oxford
2. ² Division of Immunology, Department of Pathology, University of Cambridge, Cambridge, UK

Correspondence: Dr Paul Klenerman, Peter Medawar Building for Pathogen Research, Nuffield Department Of Medicine, University of Oxford, South Parks Road, Oxford, OX1 3SY, UK. Email: paul.klenerman@medawar.ox.ac.uk

Received 28 September 2004; Accepted 6 December 2004.

Abstract

CMV-specific memory CD8⁺ T cells accumulate over time to reach high frequencies amongst peripheral blood lymphocytes – a phenomenon termed 'memory inflation'. Using tetramer staining on samples from a large number of subjects and multivariate regression analysis, we were able to relate this to the phenotype of CD8⁺ T cells. We made the following observations: (i) CD85j (ILT-2/LIR-1) was highly expressed alongside CD57 – an established effector memory marker – on CMV-specific CD8⁺ T cells; (ii) on CD8⁺ T cells as a whole, with increasing age, CD57 and CD85j (ILT-2/LIR-1) expression increased whereas CCR7 expression decreased, indicating increasing maturation of the total CD8⁺ T-cell compartment with age; (iii) unit increases in the percentage of CMV-specific CD8⁺ T cells expressing CD57 and CD85j (ILT-2/LIR-1) were associated with incremental expansion of these T-cell populations; (iv) CMV seropositivity is associated with a marked effect on the overall phenotype of CD8⁺ T cells (at any given age, CMV seropositivity is associated with an 18.7% increase in CD85j (ILT-2/LIR-1) expression); and (v) from our observations we estimated from this an apparent 'ageing effect' of CMV on CD8⁺ T cells of 35.4 years. The data presented are consistent with a predictable, unidirectional and linear model of virus specific T-cell differentiation and maturation.