Abstract
Vitamin A deficiency (VAD) has profound effects on immune responses in the gut, but its effect on other mucosal responses is less well understood. Sendai virus (SeV) is a candidate human parainfluenza virus type 1 (hPIV-1) vaccine and a candidate vaccine vector for other respiratory viruses. A single intranasal dose of SeV elicits a protective immune response against hPIV-1 within days after vaccination. To define the effect of VAD on acute responses toward SeV, we monitored both antibodies and CD8(+) T cells in mice. On day 10 following SeV infection, there was a trend toward lower antibody activities in the nasal washes of VAD mice than in those of controls, while bronchoalveolar lavage (BAL) fluid and serum antibodies were not reduced. In contrast, there was a dramatic reduction of immunodominant CD8(+) T cell frequencies in the lower respiratory tract (LRT) airways of VAD animals. These T cells also showed unusually high CD103 (the αE subunit of αEβ7) expression patterns. In both VAD and control mice, E-cadherin (the ligand for αEβ7) was better expressed among epithelial cells lining the upper respiratory tract (URT) than in LRT airways. The results support a working hypothesis that the high CD103 expression among T cell populations in VAD mice alters mechanisms of T cell cross talk with URT and LRT epithelial cells, thereby inhibiting T cell migration and egress into the lower airway. Our data emphasize that the consequences of VAD are not limited to gut-resident cells and characterize VAD influences on an immune response to a respiratory virus vaccine.