Differential impact of ageing on cellular and humoral immunity to a persistent murine γ-herpesvirus

In this study, we use the experimental mouse γ-herpesvirus model, γHV68, to investigate viral immunity in aged mice. We found no evidence of viral recrudescence or increased latent load in aged latently-infected mice, suggesting that effective immune control of γ-herpesvirus infection remains intact with ageing. As both cellular and humoral immunity have been implicated in host control of γHV68 latency, we independently examined the impact of ageing on γHV68-specific CD8 T cell function and antibody responses. Virus-specific CD8 T cell numbers and cytolytic function were not profoundly diminished with age. In contrast, whereas ELISA titers of virus-specific IgG were maintained over time, there was a progressive decline in neutralizing activity. In addition, although aged mice were able to control de novo acute infection with only slightly delayed viral clearance, serum titers of neutralizing antibody were reduced in aged mice as compared to young mice.Although there is no obvious loss of immune control of latent virus, these data indicate that ageing has differential impacts on anti-viral cellular and humoral immune protection during persistent γHV68 infection. This observation has potential relevance for understanding γ-herpesvirus immune control during disease-associated or therapeutic immunosuppression.Ageing impacts many aspects of mammalian biology, including immune function [1]. Immunological ageing is associated with a decline in the production of na？ve T and B cells, defects in the production of high-affinity antibodies, and impaired CD4 T cell function [2-5]. As a consequence, the elderly exhibit a reduced responsiveness to vaccination and an increased susceptibility to newly encountered pathogens. Although not thoroughly studied, there are also data to suggest that ageing may dampen immune control over chronic viral infections. For example, the increased incidence of herpes zoster disease in the elderly is believed to be due in part to the waning of cell-m