T_H1和T_H2细胞在痢疾疫苗诱导小鼠产生粘膜免疫应答中的调节作用

Regulative roles of T_ H1 and T _ H2 cells on mucosal immune responses of mice induced by the bivalent Shigella vaccine candidates

目的 在初步了解ＣＤ４ ＋ Ｔ 细胞参与痢疾疫苗诱导小鼠肠粘膜免疫应答的基础上，从细胞及分子水平进一步探索ＴＨ１ 和ＴＨ２ 细胞在小鼠肠粘膜对痢疾疫苗免疫应答中的调节作用。方法 以本室构建的福氏２ａ 及宋内氏双价痢疾疫苗株ＦＳ２１１７ 或ＦＳ５４１６ 灌胃免疫小鼠，从细胞表型及几种细胞因子ｍ ＲＮＡ 表达水平两方面观察小鼠肠粘膜中Ｐａｙｅｒ 氏结（ Ｐｅｙｅｒ’ｓ ｐａｔｃｈ ， ＰＰ） 及肠系膜淋巴结等免疫诱导部位ＴＨ１ 和ＴＨ２ 细胞的动态变化规律。结果 （１） 痢疾疫苗灌胃免疫后早期，小鼠肠粘膜的免疫诱导部位表现为ＴＨ１ 型细胞亚群百分率的显著降低；免疫后晚期ＴＨ１ 型细胞亚群百分率则显著升高，且高于未免疫的正常小鼠。（２） 痢疾疫苗免疫后从小鼠ＰＰ 中分离的ＣＤ４ ＋ Ｔ 细胞，在特异性痢疾疫苗抗原刺激下，先出现ＩＬ５ 、ＩＬ６ 的高表达，后出现ＩＦＮγ、ＩＬ２ 的高表达。结论 痢疾疫苗免疫后小鼠肠粘膜免疫的诱导部位早期表现为ＴＨ２ 型细胞亚群的优势活化，晚期逆转为ＴＨ１ 型细胞亚群的优势活化。

Objective Based on having known the effect of CD4 + T cells, to investigate the regulative roles of T H1 and T H2 cells on intestinal mucosal immune responses of mice induced by the bivalent Shigella vaccine candidates. Methods The mice were orally immunized with Shigella vaccine candidates, FS 2117 and FS 5416, the live attenuated bivalent hybrid strain of S. flexneri 2a and S. sonnei which were developed in this lab. In the immunized mice, the cellular phenotype dynamics and some cytokines mRNA expression level of T cells were studied with FCM and RT PCR assay. Results (1) The positive rate of T H1 cells in inductive sites of the mucosal immune system was significantly lower at the early stage, and significantly higher at the late stage after intraoral immunization than before immunization. (2) The specific antigens of the Shigella vaccine candidates induced early higher expression of IL 5 and IL 6, and late lower expression of IFN γ and IL 2 in CD4 + T cells from Peyer's patch. Conclusions Immunization of the mice with Shigella vaccine candidates can induce early preponderant activation of T H2 cells and late preponderant activation of T H1 cells in inductive sites of the intestinal mucosal immune system.