Vitamin A deficiency alters antibody forming cell and CD8+ T cell responses following intranasal vaccination with a respiratory virus vaccine (105.9)

Abstract

Abstract Vitamin A deficiency (VAD) has profound effects on immune responses in the gut, but its influence on other mucosal sites is less well understood. Sendai virus (SeV) is a candidate human parainfluenza virus type I (hPIV-1) vaccine, and a candidate vaccine vector for other respiratory viruses. A single I.N. dose of SeV elicits a protective immune response against hPIV-1 within days after vaccination. To define the effect of VAD on responses toward SeV, we monitored antibody forming cells (AFC) and immunodominant CD8+ T cells in mice. VAD inhibited SeV-specific IgA producing AFCs in the upper respiratory tract (URT) and biased the AFC response in favor of IgG-producing cells in the lower respiratory tract (LRT). In contrast, there was a dramatic reduction of CD8+ T cell frequencies in the LRT airways of VAD animals. Responding CD8+ T cells exhibited unusually high CD103 expression. In both VAD and control mice, e-cadherin (the ligand for αE(CD103)β7) was well expressed in URT tissues, but was expressed only weakly in the LRT. Results support a working hypothesis that the high CD103 expression among responding T cells in VAD mice may enhance T cell entrapment by e-cadherin and inhibit cell egress into the LRT airway. Our results highlight the concept that VAD does not exclusively affect immune responses in the gut, but has dramatic influences on immune cell function and residence in the respiratory tract.