Regulation of mucosal and systemic antibody responses by T helper cell subsets, macrophages, and derived cytokines following oral immunization with live recombinant Salmonella.
Regulation of mucosal and systemic antibody responses by T helper cell subsets, macrophages, and derived cytokines following oral immunization with live recombinant Salmonella.
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DOI：
10.4049/jimmunol.156.4.1504
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发表时间：
1996-02
影响因子：
4.4
通讯作者：
J. Vancott;H. Staats;D. Pascual;M. Roberts;S. Chatfield;M. Yamamoto;M. Coste;P. B. Carter;H. Kiyono;J. Mcghee
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文献类型：
--
作者：
J. Vancott;H. Staats;D. Pascual;M. Roberts;S. Chatfield;M. Yamamoto;M. Coste;P. B. Carter;H. Kiyono;J. Mcghee
我们评估了小鼠口服免疫表达破伤风类毒素 C 片段的重组沙门氏菌 (BRD 847) 后的调节性 Th 细胞和细胞因子反应，因为很少有信息可以解释这些载体如何诱导粘膜 IgA 反应。单剂量的 BRD 847 引发血清 IgG2a 和粘膜 IgA 抗破伤风类毒素抗体反应。为了评估 Th1 和 Th2 型反应，在体外重新刺激来自派尔氏淋巴结和脾脏的 CD4+ T 细胞，并使用细胞因子特异性 ELISPOT、ELISA 和逆转录酶 PCR 测定来评估细胞因子模式。 CD4+ T 细胞产生 IFN-γ、IL-2 以及 IL-10，但不产生 IL-4 或 IL-5。尽管 IL-6 升高，但将体外培养物中的细胞进一步纯化为 CD4+ Mac-1- T 细胞和 Mac-1+ CD4- 细胞表明，只有后者细胞群的 IL-6 基因表达持续升高，而两个分选细胞群均表现出 IFN-γ 和 IL-10 基因表达增加。因此，口服表达破伤风类毒素C片段的重组沙门氏菌在粘膜和全身组织中引起了显性的Ag特异性Th1型反应以及产生IL-10的Th2型细胞。产生 IL-6 的巨噬细胞也很明显。我们的结果与以下建议一致：Ag 特异性 Th1 细胞及其衍生的细胞因子 IFN-γ 和 IL-2，以及 Th2 衍生的 IL-10 以及巨噬细胞产生的 IL-6 在缺乏 Th2 细胞因子 IL-4 和 IL-5 优先表达的情况下为粘膜 IgA 和血清 IgG 亚类反应的发展提供重要信号。
We have assessed regulatory Th cell and cytokine responses in mice after oral immunization with recombinant Salmonella (BRD 847) expressing fragment C of tetanus toxoid, since little information is available to explain how these vectors induce mucosal IgA responses. A single dose of BRD 847 elicited serum IgG2a and mucosal IgA anti-tetanus toxoid Ab responses. To assess Th1-and Th2-type responses, CD4+ T cells from Peyer's patches and spleen were restimulated in vitro, and cytokine-specific ELISPOT, ELISA, and reverse transcriptase-PCR assays were used to assess cytokine patterns. CD4+ T cells produced IFN-gamma and IL-2 as well as IL-10, but not IL-4 or IL-5. Although IL-6 was elevated, further purification of cells from in vitro cultures into CD4+ Mac-1- T cells and Mac-1+ CD4- cells revealed that only the latter cell population had consistently elevated IL-6 gene expression, whereas both sorted populations exhibited increased IFN-gamma and IL-10 gene expression. Thus, orally administered recombinant Salmonella expressing fragment C of tetanus toxoid elicited dominant Ag-specific Th1-type responses together with Th2-type cells producing IL-10 in both mucosal and systemic tissues. Macrophages producing IL-6 were also evident. Our results are consistent with the suggestion that Ag-specific Th1 cells and their derived cytokines, IFN-gamma and IL-2, and Th2-derived IL-10 together with IL-6 produced by macrophages provide important signals for the development of mucosal IgA and serum IgG subclass responses in the absence of preferential expression of Th2 cytokines IL-4 and IL-5.