The mucosal adjuvanticity of cholera toxin involves enhancement of costimulatory activity by selective up-regulation of B7.2 expression.
The mucosal adjuvanticity of cholera toxin involves enhancement of costimulatory activity by selective up-regulation of B7.2 expression.
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DOI：
10.4049/jimmunol.159.11.5301
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发表时间：
1997-12
影响因子：
4.4
通讯作者：
Yingzi Cong;C. Weaver;C. Elson;C. Elson
中科院分区：
文献类型：
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作者：
Yingzi Cong;C. Weaver;C. Elson;C. Elson
霍乱毒素（CT）是一种强有力的粘膜免疫原和佐剂，可以强烈地引发粘膜T细胞。本研究旨在探讨CT对巨噬细胞表面共刺激分子B7.1和B7.2表达和功能活性的影响及其与CT粘膜佐剂活性的关系。通过用巨噬细胞CSF或粒细胞-巨噬细胞CSF培养骨髓来产生骨髓巨噬细胞（BMM）。在单独用CT或单独用IFN-γ处理后，BMM上的B7.2表达适度上调，并且当用CT和IFN-γ一起处理BMM时，B7.2表达进一步增加。有趣的是，CT对B7.1表达没有影响，尽管这两种分子之间的密切关系。CT对B7.2表达的上调是通过胞内cAMP的产生介导的，因为CT-B亚基没有作用，而双丁酰cAMP可以模拟这种作用。CT增加巨噬细胞对抗CD 3刺激的和同种异体刺激的T细胞的功能性共刺激活性，这种增加被抗B7.2阻断，但不被抗B7.1，Ab阻断。在体内管腔内暴露于CT后，Mac 1+派伊尔集合淋巴结细胞的B7.2表达增加。用抗B7.2抗体处理小鼠，可抑制CT的粘膜佐剂性和免疫原性。我们得出结论，CT增强了粘膜APC的共刺激活性的差异上调B7.2的表达，其粘膜佐剂性和免疫原性的影响，似乎是重要的。
Cholera toxin (CT) is a potent mucosal immunogen and adjuvant that can strongly prime mucosal T cells. The present study was undertaken to investigate the effects of CT on the expression and functional activity of the costimulatory molecules B7.1 and B7.2 on macrophages and the relationship of these effects to the mucosal adjuvanticity of CT. Bone marrow macrophages (BMM) were generated by culturing bone marrow with macrophage CSF or granulocyte-macrophage CSF. After treatment with either CT alone or IFN-gamma alone, B7.2 expression on BMM was moderately up-regulated and was further increased when BMM were treated with both CT and IFN-gamma together. Interestingly, CT had no effect on B7.1 expression despite the close relationship between these two molecules. Up-regulation of B7.2 expression by CT was mediated by intracellular cAMP production, in that CT-B subunit had no effect and dibutyryl cAMP could mimic the effect. CT increased functional costimulatory activity of macrophages for both anti-CD3-stimulated and allostimulated T cells, an increase that was blocked by anti-B7.2, but not anti-B7.1, Ab. B7.2 expression by Mac1+ Peyer's patch cells was increased after intraluminal exposure to CT in vivo. Treatment of mice with anti-B7.2 Ab in vivo inhibited both the mucosal adjuvanticity and the immunogenicity of CT. We conclude that CT enhances the costimulatory activity of mucosal APC by differentially up-regulating B7.2 expression, an effect that appears to be important for its mucosal adjuvanticity and immunogenicity.