Oral administration of ovalbumin protects mice from concanavalin A-induced hepatitis through suppression of interferon-gamma responses

Abstract

The liver is a tolerogenic organ that exhibits hypo-responsiveness to antigens circulating in the portal vein. Antigens that are orally administered at high doses reach the liver. In our previous study, we demonstrated that administering ovalbumin (OVA) orally at high doses generates unique CD4⁺ T cells and tolerogenic dendritic cells, both of which can suppress T helper type 1 (Th1) responses, in the livers of two groups of mice: DO11.10 mice with transgenic CD4⁺ T cell receptors for OVA and BALB/c mice that received OVA-specific CD4⁺ T cells through adoptive transfer. This study aimed to investigate whether oral administration of OVA at high doses inhibits the development of hepatitis in the presence of OVA-specific CD4⁺ T cells. Oral administration of OVA at high doses inhibited the development of OVA-specific and concanavalin A (Con A)-induced hepatitis in DO11.10 mice, and these effects were associated with the downregulation of Th1 responses. Furthermore, the adoptive transfer of CD4⁺ T cells from the liver of OVA-fed DO11.10 mice inhibited the development of Con A-induced hepatitis in recipient BALB/c mice through the downregulation of Th1 responses. Finally, oral administration of OVA at high doses inhibited the development of Con A-induced hepatitis in BALB/c mice bearing naïve OVA-specific CD4⁺ T cells. These results suggest that the oral administration of antigens at high doses suppresses Th1-mediated hepatitis in an antigen-non-specific manner in the presence of antigen-specific CD4⁺ T cells.

Keywords: Hepatitis; Interferon-gamma; Interleukin-4; Oral tolerance.