An Aged Mouse Model for RSV Infection and Diminished CD8+ CTL Responses

Abstract

Recent studies indicate that respiratory syncytial virus (RSV), like influenza, causes significant morbidity and mortality among elderly persons. There are currently no animal models to study the effects of aging on RSV disease and immunity. This manuscript provides an initial description of such a model. Aged and young BALB/c mice (22-24 and 2-4 months, respectively) were infected with 10⁴ TCID₅₀ of RSV A2. RSV was detected by culture in lung and nose wash specimens obtained 4-6 days following infection at a slightly higher titer in old mice in comparison with young mice. RT-PCR assay detected RSV in the lungs and nose washes of all mice on 4, 8, and 21 days postinoculation, with only a slightly less frequency in young mice. Splenic lymphocytes from old mice exhibited significantly lower RSV-specif ic MHC class I-restricted CD8⁺ CTL responses (P < 0.01-0001), and reduced IFN-production (P < 0.03) than young mice. Conversely, IL-4 production was somewhat elevated in old mice. These results demonstrate diminished RSV virus-specific CD8⁺ CTL responses and IFN-γ production in old mice in comparison with young. It is speculated that the deficient RSV-specific CTL responses may account for the Increased morbidity and mortality from RSV Infections in elderly persons. Although detailed hlstopathological, virological, and immunological analyses are incomplete at present, the old BALB/c RSV infection model described provides an opportunity to evaluate the role of CD8+ CTL and cytokines in RSV disease in aging.