Oral Adjuvants Which Enhance or Replace T Cells for IgA Responses

Abstract

Abstract Oral administration of T-dependent (TD) antigens leads to sensitization of lymphoreticular cells, including regulatory T cells, IgA committed B cells and accessory cells in Peyer's patches (PP) and subsequent IgA responses in distant mucosal tissues. Oral adjuvants such as concanavalin A (Con A), peptidoglycan (PG) and muramyl dipeptide (MDP) can potentiate IgA responses to TD antigens, e.g., oral administration of Con A and antigen induces T helper (Th) cells in PP which augment IgA responses. Bacterial cell wall components, e.g., PG and MDP, may replace T cell-derived factors for B cell growth and differentiation into antibody synthesizing cells. When athymic nude mice were systemically immunized with sheep erythrocytes (SRBC) and MDP or PG, good splenic IgM anti-SRBC plaque-forming cell (PFC) responses were seen. In addition, PG supported in vitro anti-SRBC PFC responses in T cell depleted spleen cell cultures from nude and normal mice. When nude mice were given SRBC and PG or MDP orally for two days, followed by intraperitoneal injection of SRBC and PG (or MDP) 7 days later, significant salivary IgA antibody responses were seen. Identically treated normal mice exhibited higher salivary IgA antibody responses than mice immunized with antigen alone. These results indicate that PG and MDP possess T cell-replacing factor (TRF)-like activity for B cell responses to TD antigens in the absence of mature T cells. Thus, MDP and PG can be used as oral adjuvants for the induction and enhancement of IgA responses in both athymic nude and normal mice.