Does memory improve with age? CD85j (ILT-2/LIR-1) expression on CD8 T cells correlates with 'memory inflation' in human cytomegalovirus infection.
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.
Northfield
John
J
Peter Medawar Building for Pathogen Research, Nuffield Department Of Medicine, University of Oxford, South Parks Road, Oxford, UK.
Lucas
Michaela
M
Jones
Helena
H
Young
Neil T
NT
Klenerman
Paul
P
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015415:Biomarkers; D018959:CD57 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology*; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
D015703:Antigens, CD; D015415:Biomarkers; D018959:CD57 Antigens; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic