Infection with cytomegalovirus but not herpes simplex virus induces the accumulation of late-differentiated CD4+ and CD8+ T-cells in humans

• Published in: Journal of general virology 2011-12, Vol.92 (Pt 12), p.2746-2756
• Main Authors: DERHOVANESSIAN, Evelyna, MAIER, Andrea B, HÄHNEL, Karin, BECK, Robert, DE CRAEN, Anton J. M, SLAGBOOM, Eline P, WESTENDORP, Rudi G. J, PAWELEC, Graham
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; CD28 Antigens - analysis; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD4-Positive T-Lymphocytes - virology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; CD8-Positive T-Lymphocytes - virology; Cell Differentiation; Cytomegalovirus - growth & development; Cytomegalovirus Infections - immunology; Cytomegalovirus Infections - pathology; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Humans; Leukocyte Common Antigens - analysis; Male; Microbiology; Middle Aged; Miscellaneous; Receptors, CCR7 - metabolism; Simplexvirus - growth & development; T-Lymphocyte Subsets - immunology; Tumor Necrosis Factor Receptor Superfamily, Member 7 - analysis; Virology
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.036004-0

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.