Does memory improve with age? CD85j (ILT-2 LIR-1) expression on CD8 T cells correlates with 'memory inflation' in human cytomegalovirus infection

• Published in: Immunology and cell biology Vol. 83; no. 2; pp. 182 - 188
• Main Authors: Northfield, John, Lucas, Michaela, Jones, Helena, Young, Neil T, Klenerman, Paul
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.04.2005; Blackwell Science Ltd
• Subjects: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Aging - immunology; Antigens, CD - biosynthesis; Antigens, CD - genetics; Antigens, CD - immunology; Biomarkers; CD57 Antigens - immunology; CD8+ T cell; CD8-Positive T-Lymphocytes - immunology; CD85j (ILT‐2; Cell Proliferation; CMV; Cytomegalovirus - immunology; Cytomegalovirus Infections - immunology; Humans; Immunologic Memory - genetics; Immunologic Memory - immunology; Leukocyte Immunoglobulin-like Receptor B1; LIR‐1; memory inflation; Middle Aged; Receptors, Immunologic - biosynthesis; Receptors, Immunologic - genetics; Receptors, Immunologic - immunology
• ISSN: 0818-9641; 1440-1711
• DOI: 10.1111/j.1440-1711.2005.01321.x

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.