共刺激分子B7-H4在小鼠食管癌前病变进展中脾淋巴细胞表面的表达

Expression of costimulatory molecule B7-H4 on spleen lymphocytes during the progression of precancerous lesions in esophagus in mice

目的 :探讨小鼠食管癌前病变进展的不同阶段脾淋巴细胞中CD4+T细胞、CD8+T细胞和调节性T细胞[CD4+CD25+叉头翼状旋转转录因子3(forkhead-winged helix transcription factor 3,foxp3)+]所占比例及共刺激分子B7同系物4(B7 homologue 4,B7-H4)的表达变化。方法 :应用4-硝基喹啉-N-氧化物(4-nitroquinoline-N-oxide,4NQO)饮水法诱导建立小鼠食管癌前病变模型,通过苏木精-伊红(hematoxylin-eosin,HE)染色评价不同阶段小鼠食管组织的病理变化,应用FCM法检测食管癌前病变不同阶段小鼠脾淋巴细胞中CD4+T细胞、CD8+T细胞和CD4+CD25+foxp3+调节性T细胞所占的百分率,以及B7-H4在上述细胞表面的阳性表达率。结果 :4NQO诱癌模型组小鼠食管组织在诱癌第12周出现低级别上皮内瘤变,并随着诱癌时间的延长,出现高级别上皮内瘤变和原位癌。4NQO诱癌模型组脾淋巴细胞中CD4+T细胞和CD4+CD25+foxp3+调节性T细胞所占百分率明显高于对照组(以蒸馏水为饮用水)(P均<0.01)。4NQO诱癌模型组小鼠CD4+T细胞上B7-H4的阳性表达率明显高于对照组(P<0.01),并且具有时间依赖性(P<0.05)。结论 :4NQO饮水法能够诱导小鼠发生食管癌前病变,CD4+T细胞、调节性T细胞以及B7-H4可能参与了机体的免疫逃逸机制。

Objective：To investigate the percentages of splenic CD4＋T,CD8＋T and CD4＋CD25＋ forkhead-winged helix transcription factor 3（foxp3）＋ T regulatory cells and the expression of costimulatory molecule B7 homologue 4（B7-H4） during different stages of progression of precancerous lesions in esophagus in mice.Methods：4-Nitroquinoline-N-oxide（4NQO） in drinking water was used to induce esophageal precancerous conditions in mice.The hematoxylin-eosin（HE） staining was used to evaluate the pathological changes in different stages of precancerous conditions.The percentages of CD4＋T,CD8＋T and CD4＋CD25＋foxp3＋ T regulatory cells in splenic lymphocytes and the positive rates of B7-H4 expression on CD4＋T,CD8＋T and CD4＋CD25＋foxp3＋ T regulatory cells in mice in different stages of esophageal precancerous conditions were detected by fl ow cytometry（FCM）.Results：At the time of the 12 th week of giving 4-NQO in drinking water to induce esophageal cancer,the pathological abnormalities with low-grade intraepithelial neoplasia occurred in esophageal tissues in mice,and the high-grade intraepithelial neoplasia and carcinoma in situ were developed along with the time.The percentages of CD4＋T and CD4＋CD25＋foxp3＋ T regulatory cells in splenic lymphocytes in mice induced by drinking of 4-NQO were higher than those in the control mice（by drinking of distilled water）（both P 〈 0.01）.As compared with the control mice,the positive rate of B7-H4 on the CD4＋T cells in mice induced by drinking of 4-NQO was higher（P 〈 0.01） in a time-dependent manner（P 〈 0.05）.Conclusion：Giving 4-NQO in drinking water can induce esophageal precancerous lesions in mice.CD4＋T cells,T regulatory cells and B7-H4 may be involved in tumor immune escape mechanism.