Expression of T-cell Immunoglobulin- and Mucin-domain-containing Molecules-1 and-3 (Tim-1 and Tim-3) in Helicobacter pylori Infection
Expression of T-cell Immunoglobulin- and Mucin-domain-containing Molecules-1 and-3 (Tim-1 and Tim-3) in Helicobacter pylori Infection
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DOI：
10.1111/j.1523-5378.2011.00855.x
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发表时间：
2011-10-01
期刊：
影响因子：
4.4
通讯作者：
Lv, Nonghua
中科院分区：
文献类型：
--
作者：
Hu, Sijun;Xie, Yong;Lv, Nonghua
背景：免疫应答在幽门螺杆菌感染中起重要作用。Tim-1和Tim-3分别在终末分化的Th2和Th1细胞上表达，参与调节Th免疫应答。到目前为止，Tim在幽门螺杆菌感染中的作用仍不清楚。材料与方法：(1)将BALB/c小鼠脾淋巴细胞与不同浓度的活菌幽门螺杆菌共培养。或者用活的幽门螺杆菌攻毒小鼠，建立幽门螺杆菌感染模型。(2)采用RT-PCR法检测小鼠淋巴细胞和脾脏中Tim-1和Tim-3 mRNA水平的表达。流式细胞术检测tim -3阳性细胞百分比。采用标准夹心细胞因子ELISA法检测上清液中细胞因子的产生。结果：(1)共培养：与正常对照相比，与幽门螺杆菌共培养的淋巴细胞在12 h时Tim-1的产生明显减少，Tim-3的产生明显增加。Th2细胞因子的表达变化趋势与Tim-1相似；另外，Th1细胞因子的表达变化趋势与Tim-3相似。(2)感染：与对照组相比，感染小鼠体内Tim-1表达降低；相比之下，Tim-3表达增加。脾脏中Tim-1和Tim-3 mRNA的表达分别与胃匀浆上清中Th2和Th1细胞因子水平呈显著正相关。结论：幽门螺杆菌可抑制T淋巴细胞向Th2细胞分化，促进Th1细胞分化，诱导Th1偏向性免疫反应。Tim-1和Tim-3的表达可分别反映Th2和Th1的免疫应答，为通过调节Tim-1和Tim-3预防和治疗幽门螺杆菌感染及相关疾病提供依据。
Background: Th immune response plays an important role in Helicobacter pylori (H. pylori) infection. Tim-1 and Tim-3 are expressed on terminally differentiated Th2 and Th1 cells, respectively, and participate in the regulation of Th immune response. Until now, the role of Tim in H. pylori infection remains unclear.Materials and Methods: (1) Lymphocytes isolated from the spleen of BALB/c mice were co-cultured with different concentrations of viable H. pylori. Alternatively, mice were challenged by viable H. pylori to set up the H. pylori infection model. (2) The expression of Tim-1 and Tim-3 on mRNA level in lymphocytes or spleen of mice was determined by RT-PCR. The percentage of Tim-3-positive cells was determined by flow cytometric analysis. The production of cytokine in supernatants was measured by standard sandwich cytokine ELISA.Results: (1) Co-culture: At 12 hours, there was markedly decreased production of Tim-1 and increased production of Tim-3 in lymphocytes co-cultured with H. pylori compared with normal control. The change of Th2 cytokine had the similar tendency as that of Tim-1 expression; alternatively, the change of Th1 cytokine had the similar tendency as that of Tim-3 expression. (2) Infection: Tim-1 expression was declined in infected mice compared with control group; in the contrast, Tim-3 expression was increased. Furthermore, the expression of Tim-1 and Tim-3 mRNA in spleen was significantly positively correlated with the level of Th2 and Th1 cytokine in gastric homogenized supernatant, respectively.Conclusion: H. pylori could inhibit the differentiation of T lymphocytes toward Th2 cells, promote the Th1 cell differentiation, and induce Th1-biased immune response. The expression of Tim-1 and Tim-3 could reflect Th2 and Th1 immune response, respectively, which provide evidence for the prevention and treatment of H. pylori infection and correlation diseases through regulation of Tim-1 and Tim-3.