Research

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

Eric J. Yager , In-Jeong Kim , Michael L. Freeman , Kathleen G. Lanzer , Claire E. Burkum , Tres Cookenham , David L. Woodland and Marcia A. Blackman

Immunity & Ageing 2010, 7:3doi:10.1186/1742-4933-7-3

Published:	2 February 2010

Abstract (provisional)

Background

Oncogenic gamma-herpesviruses establish life-long infections in their hosts and control of these latent infections is dependent on continual immune surveillance. Immune function declines with age, raising the possibility that immune control of gamma-herpesvirus infection becomes compromised with increasing age, allowing viral reactivation and/or increased latent load, both of which are associated with the development of malignancies.

Results

In this study, we use the experimental mouse gamma-herpesvirus model, gammaHV68, 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 gamma-herpesvirus infection remains intact with ageing. As both cellular and humoral immunity have been implicated in host control of gammaHV68 latency, we independently examined the impact of ageing on gammaHV68-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.

Conclusion

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 gammaHV68 infection. This observation has potential relevance for understanding gamma-herpesvirus immune control during disease-associated or therapeutic immunosuppression.