Does memory improve with age? CD85j (ILT‐2/LIR‐1) expression on CD8+ T cells correlates with ‘memory inflation’ in human cytomegalovirus infection

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.