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

在这项研究中，我们研究了天然霍乱毒素（nCT）作为鼻佐剂是否可以支持三硝基苯基（TNP）-脂多糖（LPS）特异性粘膜免疫应答。在存在或不存在nCT的情况下，给予C57 BL/6小鼠鼻TNP-LPS。在免疫后5天，显着更高水平的TNP-特异性粘膜伊加抗体（Ab）反应诱导的鼻洗液，唾液和血浆中的小鼠给予nCT + TNP-LPS比那些在TNP-LPS单独。另外。还观察到给予nCT加TNP-LPS的小鼠血浆中IgG 3和IgM Ab的增强。在给予nCT的小鼠的鼻道（NP）、下颌下腺（SMG）和鼻咽相关淋巴网状组织等粘膜组织中也检测到大量的TNP特异性伊加Ab形成细胞（AFC）。在流式细胞术分析中，在鼻给予TNP-LPS + nCT的小鼠的SMG和NP中观察到比仅给予TNP-LPS的小鼠的SMG和NP中的表面伊加^+、CD 5 ^+ B细胞（B-la B细胞）的数量更高。此外，鼻内给予TNP-LPS加nCT的小鼠的SMG和NP中的B-la B细胞表达IL-5受体α链（IL-5 R α）水平增加。因此。来自这些粘膜效应淋巴组织的CD 4 ^+ T细胞在蛋白质和mRNA水平上都能产生高水平的IL-5。当用抗IL-5单克隆抗体治疗小鼠时，在外部分泌物中注意到TNP特异性粘膜伊加Ab应答的显著减少。这些发现表明，鼻nCT作为佐剂可增强粘膜对T细胞非依赖性抗原的免疫应答，这是由于粘膜效应淋巴组织中IL-5 R α^+ B-la B细胞和产生IL-5的CD 4 ^+T细胞之间的相互作用。

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.