Rudimentary signs of immunosenescence in Cytomegalovirus-seropositive healthy young adults

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 m²) 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.