目的：探讨Toll 受体1/2(Toll like receptor 1/2, TLR1/2)信号对荷瘤小鼠来源的CD8+T细胞功能的影响及其可能机制。方法：利用小鼠Lewis肺癌细胞株3LL建立小鼠肺癌荷瘤模型，MACS分选小鼠脾CD8+T细胞；体外经PBS或TLR1/2激动剂BLP刺激后，Real-time PCR和流式细胞术分别从基因和蛋白水平检测CD8+T细胞的TLR分子表达；用ELISA和流式细胞术检测经PBS或BLP刺激后的CD8+T细胞分泌细胞因子和增殖的能力，并用关键信号分子抑制剂分析可能的分子机制。结果：与PBS对照组相比，TLR1/2激动剂BLP不但有效上调荷瘤机体CD8+T细胞TLR1和TLR2分子的基因水平\[TLR1：（0.353±0.015） vs （0101±0.017），P<0.01；TLR2：（0.232±0.031） vs （0.080±0.004），P<0.05\]及蛋白水平（P<0.05），而且显著促进CD8+T细胞分泌功能性细胞因子\[IFN-γ：（2 375±305） vs （850±50），P<0.05；IL-2：（1 600±200） vs （350±50），P<0.05\]和增殖的能力（P<0.05），这一效应依赖于NF-κB和P38通路。结论： TLR1/2信号直接作用于荷瘤小鼠的CD8+T细胞并促进其功能，该研究既丰富了TLR的作用范围，也为基于TLR激动剂的肿瘤生物治疗提供了实验依据。

Objective:To investigate the effect of Toll like receptor 1/2(TLR1/2) signaling on CD8+T cells derived from 3LL tumor-bearing mice and its underlying mechanisms. Methods:3LL Lewis lung carcinoma cell line was used to establish tumor-bearing mice model, of which CD8+T cells were purified from the spleen by MACS. CD8+T cells were stimulated in vitro with PBS or TLR1/2 agonist, BLP, and then the gene and protein expression levels of TLRs in CD8+T cells were measured by Real-time PCR and Flow cytometry. What’s more, cytokine secretion and proliferation of CD8+T cells after PBS or BLP stimulation were detected by ELISA and Flow cytometry. The inhibitors of key signal molecules were used to explore the underlying mechanisms of BLP influencing CD8+T cells derived from 3LL-bearing mice. Results: Compared with PBS group, BLP not only greatly increased the expressions of TLR1 and TLR2 genes (TLR1: \[0.353±0.015\] vs \[0.101±0017\], P<0.01; TLR2: (\[0.232±0.031\] vs \[0.080±0.004\], P<0.05) and proteins (P<0.05), but also significantly enhanced the functional cytokine secretion (IFN-γ: \[2 375±305\] vs \[850±50\], P<0.05；IL-2: \[1 600±200\] vs \[350±50\]，P<0.05); in addition, it promoted the proliferation of CD8+T cells (P<0.05). All of these were dependent on NF-κB and P38 pathways. Conclusion: TLR1/2 signaling could directly promote the functions of CD8+T cells derived from 3LL-tumor bearing mice, which might enrich the scope of TLRs and also provide the basis for TLR agonist-based tumor immunotherapy.

国家自然科学基金资助项目（No. 31570892，No.31400772）