title: Rudimentary signs of immunosenescence in Cytomegalovirus-seropositive healthy young adults.
abstract: Ageing is associated with a decline in immune competence termed immunosenescence. In the elderly, this process results in an accumulation of differentiated 'effector' phenotype memory T cells, predominantly driven by Cytomegalovirus (CMV) infection. Here, we asked whether CMV also drives immunity towards a senescent profile in healthy young adults. One hundred and fifty-eight individuals (mean ± SD; age 21 ± 3 years, body mass index 22.7 ± 2.7 kg m(2)) were assessed for CMV serostatus, the numbers/proportions of CD4(+) and CD8(+) late differentiated/effector memory cells (i.e. CD27(-)CD28(-)/CD45RA(+)), plasma interleukin-6 (IL-6) and antibody responses to an in vivo antigen challenge (half-dose influenza vaccine). Thirty percent (48/158) of participants were CMV(+). A higher lymphocyte and CD8(+) count (both p < 0.01) and a lower CD4/CD8 ratio (p < 0.03) were observed in CMV(+) people. Eight percent (4/58) of CMV(+) individuals exhibited a CD4/CD8 ratio <1.0, whereas no CMV(-) donor showed an inverted ratio (p < 0.001). The numbers of CD4(+) and CD8(+)CD27(-)CD28(-)/CD45RA(+) cells were ~ fourfold higher in CMV(+) people (p < 0.001). Plasma IL-6 was higher in CMV(+) donors (p < 0.05) and showed a positive association with the numbers of CD8(+)CD28(-) cells (p < 0.03). Finally, there was a significant negative correlation between vaccine-induced antibody responses to the A/Brisbane influenza strain and CMV-specific immunoglobulin G titres (p < 0.05). This reduced vaccination response was associated with greater numbers of total CD8(+) and CD4(+) and CD8(+)CD27(-)CD28(-)/CD45RA(+) cells (p < 0.05). This study observed marked changes in the immune profile of young adults infected with CMV, suggesting that this virus may underlie rudimentary aspects of immunosenescence even in a chronologically young population.
authors.affiliation: School of Sport and Exercise Sciences, University of Birmingham, Birmingham, UK, j.e.turner@bham.ac.uk.
authors.forename: James E
authors.initials: JE
authors.lastname: Turner
authors.forename: John P
authors.initials: JP
authors.lastname: Campbell
authors.forename: Kate M
authors.initials: KM
authors.lastname: Edwards
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Howarth
authors.forename: Graham
authors.initials: G
authors.lastname: Pawelec
authors.forename: Sarah
authors.initials: S
authors.lastname: Aldred
authors.forename: Paul
authors.initials: P
authors.lastname: Moss
authors.forename: Mark T
authors.initials: MT
authors.lastname: Drayson
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Burns
authors.forename: Jos A
authors.initials: JA
authors.lastname: Bosch
mesh_terms: D000375:Aging / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood; D016516:CD4-CD8 Ratio; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016130:Immunophenotyping; D007252:Influenza Vaccines / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D015850:Interleukin-6