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目的:研究小鼠肿瘤发生早期两型含T细胞免疫球蛋白及黏蛋白结构域的分子3(Tim3)的表达特点,以及与免疫调节相关基因表达的时空关系,并探讨其在诱导肿瘤免疫耐受中的作用。方法:建立小鼠实体瘤模型,采用RTPCR法检测肿瘤组织中可溶型Tim3(sTim3)和膜型Tim3(flTim3),以及叉头盒P3(forkheadboxP3,Foxp3)、细胞毒性T淋巴细胞抗原4(CTLA4)、糖皮质激素诱导的肿瘤坏死因子受体家族相关受体(GITR)、TGFβ、IL10和IFNγ等在不同时相的表达及相应时相肿瘤的生长情况。结果:在早期的肿瘤组织中,sTim3的表达先于flTim3,其后flTim3大量表达,而sTim3的表达则下调直至消失。Foxp3和GITR随flTim3同时表达并逐步上调。CTLA4的表达先于flTim3,并随着时间的推移表达上调。flTim3同Foxp3的表达具有空间位置的一致性。flTim3、Foxp3和CTLA4的表达水平同肿瘤的生长呈正相关。结论:随着肿瘤不断的生长,肿瘤局部的免疫应答逐渐趋向于负调节。flTim3在诱导肿瘤免疫耐受的过程中发挥着重要作用,而sTim3可能起着不同的作用。
OBJECTIVE: To study the expression of Tim3, an early type of tumor-bearing T-cell immunoglobulin and mucin domain in mice and its temporal and spatial relationship with the expression of immunoregulation-related genes and to explore its role in the induction of tumor immunity By the role. Methods: The mouse solid tumor model was established. The soluble Tim3 (sTim3) and membrane type Tim3 (flTim3) and forkhead box P3 (Foxp3), cytotoxic T lymphocyte antigen 4 CTLA4), glucocorticoid-induced tumor necrosis factor receptor family related receptor (GITR), TGFβ, IL10 and IFNγ in different phases and the corresponding time-phase tumor growth. RESULTS: In early tumor tissues, sTim3 was expressed prior to flTim3, followed by flTim3 expression, whereas sTim3 expression was down-regulated until disappearance. Foxp3 and GITR with flTim3 simultaneously expressed and gradually increased. CTLA4 expression preceded flTim3 and was up-regulated over time. The expression of flTim3 and Foxp3 has spatial consistency. The expression levels of flTim3, Foxp3 and CTLA4 were positively correlated with tumor growth. Conclusion: With the continuous growth of tumor, the local immune response gradually tends to negative regulation. flTim3 plays an important role in inducing tumor immune tolerance, whereas sTim3 may play different roles.