Elucidation of function of cholera toxin as a mucosal adjuvant in salivary IgA production to T-cell independent antigen

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In this study, we examined whether native cholera toxin (nCT) as a nasal adjuvant could support' trinitrophenyl (TNP)-lipopolysaccharide (LPS)-specific mucosal immune responses. C57BL/6 mice were given nasal TNP-LPS in the presence or absence of nCT. On 5 days after immunization, significantly higher levels of TNP-specific mucosal IgA antibody (Ab) responses were induced in the nasal washes, sal iva and plasma of mice given nCT plus TNP-LPS than in those given TNP-LPS alone. In addition. Enhanced IgG3 and IgM Ab in the plasma of mice given nCT plus TNP-LPS were also seen. High numbers of TNP-specific IgA Ab forming cells (AFCs) were also detected in mucosal tissues such as the nasal passages (NPs), the submandibular glands (SMGs) and nasopharyngeal-associated lymphoreticular tissue of mice given nCT. In the flow cytometric analysis, higher numbers of surface IgA^+,CD5^+ B cells (B-la B cells) in SMGs and NPs of mice given nasal TNP-LPS plus nCT than in those given TNP-LPS alone were seen. Further, increased levels of IL-5 receptor α chain (IL-5Rα) were expressed by B-la B cells in SMGs and NPs of mice given nasal TNP-LPS plus nCT. Thus. CD4^+ T cells from these mucosal effector lymphoid tissues produce high levels of IL-5 at both protein and mRNA levels. When mice were treated with anti-IL-5 monoclonal Ab, significant reductions in TNP-specific mucosal IgA Ab responses were noted in external secretions. These findings show that nasal nCT as an adjuvant enhances mucosal immune responses to a T cell independent antigen due to the cross-talk between IL-5Rα^+ B-la B cells and IL-5 producing CD4^+T cells in the mucosal effector lymphoid tissues.