Mucosal Immunity in CD4-Deficient Mice : Direct Evidence for Mucosal IgA Antibody Responses

Abstract

CD4⁺ T cells and their derived cytokines are major contributors to the induction and regulation of antigen-specific antibody responses in both mucosal and systemic compartments. Past studies have shown that antigen-specific mucosal immune responses are impaired in CD4 gene-disrupted (CD4^-/-) mice ; however, surface IgA⁺ B cells are found to co-localize to the germinal center area and CD4^-CD8^- (double negative) T cells replace CD4⁺ T cells in the Peyer's patches. Thus, we investigated whether different oral delivery systems could elicit mucosal immunity. Here we show that CD4^-/- mice are capable of eliciting secretory IgA antibody responses. Oral immunization using tetanus toxoid (TT) with cholera toxin as a mucosal adjuvant resulted in mucosal IgA and serum IgG anti-TT antibody responses. Furthermore, antigen-specific T cell proliferative responses showed that significant TT-specific proliferative responses were induced in the CD4^-CD8^-, but not CD4^-CD8⁺, T cells from Peyer's patches of CD4^-/- mice given TT plus cholera toxin orally. These results suggest that antigen-specific mucosal IgA antibody responses may be induced by CD4^-CD8^- T cells in the absence of CD4⁺ T cells.