Oral Immunization with Recombinant Salmonella Induces Mucosal IgA Antibodies in CD4-Deficient Mice

Abstract

It is well established that CD4⁺ T cells are major contributors to the induction and regulation of antigen-specific antibody responses in both mucosal and systemic compartments. However, our previous studies have demonstrated that oral immunization of CD4^-/- mice with soluble protein plus cholera toxin as adjuvant elicited antigen-specific IgA antibody responses in the gastrointestinal tract. In this study, we investigated whether oral delivery of live bacteria could elicit mucosal immunity in CD4^-/- mice. Oral immunization with recombinant Salmonella expressing fragment C of tetanus toxin resulted in serum IgG and IgA anti-tetanus toxoid antibody responses. Furthermore, CD4^-/- mice are capable of eliciting secretory IgA antibodies in the intestinal tract. Antibody-forming cell analysis confirmed the antibody titers by revealing significant numbers of tetanus toxoid-specific IgG- and IgA-forming cells in the spleen and IgA-forming cells in intestinal lamina propria. In addition, significant delayed-type hypersensitivity responses were detected in CD4^-/- mice given rSalmonella-Tox C. These results suggest that antigen-specific mucosal as well as systemic antibody responses can be induced in the absence of CD4⁺ T cells after oral immunization with Salmonella.