Aged mice exhibit a severely diminished CD8 T cell response following respiratory syncytial virus infection

J Virol. 2013 Dec;87(23):12694-700. doi: 10.1128/JVI.02282-12. Epub 2013 Sep 18.

Abstract

Respiratory virus infections in the elderly result in increased rates of hospitalization and death. Respiratory syncytial virus (RSV) is a leading cause of severe virus-induced respiratory disease in individuals over the age of 65. CD8 T cells play a critical role in mediating RSV clearance. While it is clear that T cell immunity declines with age, it is not clear to what extent the CD8 T cell response to RSV is altered. Using aged BALB/c mice, we demonstrated that RSV-specific CD8 T cell responses were significantly reduced in the lungs of aged mice at the peak of the T cell response and that this decrease correlated with delayed viral clearance. Despite a decrease in the overall numbers of RSV-specific CD8 T cells during acute infection, their capacity to produce effector cytokines was not impaired. Following viral clearance, the RSV-specific memory CD8 T cells were similar in total number and phenotype in young and aged mice. Furthermore, following infection with a heterologous pathogen expressing an RSV epitope, RSV-specific memory CD8 T cells exhibited similar activation and ability to provide early control of the infection in young and aged mice. These data demonstrate a decrease in the capacity of aged mice to induce a high-magnitude acute CD8 T cell response, leading to prolonged viral replication, which may contribute to the increased disease severity of RSV infection observed for aged individuals.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / immunology*
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Down-Regulation
  • Female
  • Humans
  • Lung / immunology
  • Lung / virology
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Viruses / immunology
  • Respiratory Syncytial Viruses / physiology*
  • Th2 Cells / immunology