Nasal cholera toxin elicits IL-5 and IL-5 receptor α-chain expressing B-1a B cells for innate mucosal IgA antibody responses
Nasal cholera toxin elicits IL-5 and IL-5 receptor α-chain expressing B-1a B cells for innate mucosal IgA antibody responses
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DOI：
10.4049/jimmunol.178.10.6058
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发表时间：
2007-05-15
影响因子：
4.4
通讯作者：
Fujihashi, Kohtaro
中科院分区：
文献类型：
--
作者：
Kataoka, Kosuke;Fujihashi, Keiko;Fujihashi, Kohtaro
在这项研究中，我们研究是否天然霍乱毒素（nCT）作为粘膜佐剂可以支持三硝基苯基（TNP）-LPS特异性粘膜免疫反应。在存在或不存在nCT的情况下，给予C57 BL/6小鼠鼻TNP-LPS。五天后，显着更高水平的TNP-特异性粘膜伊加抗体反应诱导的鼻洗液，唾液和血浆中的小鼠给予nCT + TNP-LPS比那些只给予TNP-LPS。在给予nCT的小鼠的粘膜组织如鼻通道（NP）、下颌下腺（SMG）和鼻咽相关淋巴网状组织中也检测到大量的TNP特异性伊加Ab形成细胞。流式细胞术分析显示，鼻内给予TNP-LPS + nCT的小鼠SMG和NP中表面伊加（+）、CD 5（+）B细胞（B-la B细胞）的数量高于单独给予TNP-LPS的小鼠。此外，给予鼻TNP-LPS加nCT的小鼠的SMG和NP中的B-1a B细胞表达增加水平的IL-5 R α-链。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水平上产生高水平的IL-5。当用抗IL-5 mAb处理小鼠时，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作为佐剂增强了对T细胞非依赖性Ag的粘膜免疫应答，这是由于粘膜效应淋巴组织中IL-5 Ra（+）B-la B细胞和产生IL-5的CD 4（+）T细胞之间的串扰。免疫学杂志，2007，178：6058-6065.
In this study, we examine whether native cholera toxin (nCT) as a mucosal adjuvant can support trinitrophenyl (TNP)-LPS-specific mucosal immune responses. C57BL/6 mice were given nasal TNP-LPS in the presence or absence of nCT. Five days later, significantly higher levels of TNP-specific mucosal IgA Ab responses were induced in the nasal washes, saliva, and plasma of mice given nCT plus TNP-LPS than in those given TNP-LPS alone. ffigh numbers of TNP-specific IgA Ab-forming cells 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. Flow cytometric analysis showed that 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. Furthermore, increased levels of IL-5R a-chain were expressed by B-1a 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 mAb, 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 Ag due to the cross-talk between IL-5Ra(+) B-la B cells and IL-5-producing CD4(+) T cells in the mucosal effector lymphoid tissues. The Journal of Immunology, 2007, 178: 6058-6065.