title: Infection with cytomegalovirus but not herpes simplex virus induces the accumulation of late-differentiated CD4+ and CD8+ T-cells in humans.
abstract: Human cytomegalovirus (CMV) establishes persistent, usually asymptomatic, infection in healthy people. Because CMV infection is associated with the presence of lower proportions of peripheral naïve CD8+ T-cells and a higher fraction of late-differentiated CD8+ cells, commonly taken as biomarkers of age-associated compromised adaptive immunity ('immunosenescence'), we asked whether chronic exposure to any persistent virus mediates these effects. Herpes simplex virus (HSV) is also a widespread herpesvirus that establishes lifelong persistence, but, unlike CMV, its impact on the distribution of T-cell subsets has not been established. Here, we analysed T-cell subsets in 93 healthy people aged 42-81 years infected or not infected with CMV and/or HSV. Individuals harbouring CMV were confirmed to possess lower frequencies of naïve CD8+ T-cells (defined as CD45RA+CCR7+CD27+CD28+) and greater proportions of late-differentiated effector memory (CD45RA-CCR7-CD27-CD28-) and so-called TEMRA (CD45RA+CCR7-CD27-CD28-) CD4 and CD8 subsets, independent of HSV seropositivity. In CMV-seronegative donors, HSV did not affect T-cell subset distribution significantly. We conclude that these hallmarks of age-associated alterations to immune signatures are indeed observed in the general population in people infected with CMV and not those infected with a different persistent herpesvirus.
authors.affiliation: Department of Internal Medicine II, Centre for Medical Research, University of Tübingen, Tübingen, Germany.
authors.forename: Evelyna
authors.initials: E
authors.lastname: Derhovanessian
authors.affiliation: Netherlands Consortium for Healthy Aging, Leiden University Medical Centre, Leiden, The Netherlands.|Department of Gerontology and Geriatrics, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Maier
authors.affiliation: Department of Internal Medicine II, Centre for Medical Research, University of Tübingen, Tübingen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Hähnel
authors.affiliation: Institute of Medical Virology, University of Tübingen, Tübingen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Beck
authors.affiliation: Netherlands Consortium for Healthy Aging, Leiden University Medical Centre, Leiden, The Netherlands.|Department of Gerontology and Geriatrics, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Anton J M
authors.initials: AJM
authors.lastname: de Craen
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands.|Netherlands Consortium for Healthy Aging, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Eline P
authors.initials: EP
authors.lastname: Slagboom
authors.affiliation: Netherlands Consortium for Healthy Aging, Leiden University Medical Centre, Leiden, The Netherlands.|Department of Gerontology and Geriatrics, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Rudi G J
authors.initials: RGJ
authors.lastname: Westendorp
authors.affiliation: Department of Internal Medicine II, Centre for Medical Research, University of Tübingen, Tübingen, Germany.
authors.forename: Graham
authors.initials: G
authors.lastname: Pawelec
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018106:CD28 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002454:Cell Differentiation; D003587:Cytomegalovirus / Q000254:growth & development*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D008875:Middle Aged; D054400:Receptors, CCR7 / Q000378:metabolism; D018139:Simplexvirus / Q000254:growth & development*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
chemical_list: D018106:CD28 Antigens; D054400:Receptors, CCR7; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens