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聚肌胞对活化早期T细胞PD-1表达的诱导及对黑色素瘤生长的抑制作用

Polyinosinic-polycytidylic Acid Mediates PD-1 Expression in T Cells at Early Stage of Activation and Inhibits Melanoma Growth

  • 摘要:
    目的 探讨活化早期阶段(脾组织内,未向靶器官迁移的)T细胞程序性死亡受体1(PD-1)表达情况。
    方法 6~8周龄C57BL/6小鼠随机分组后,以Poly I:C肽疫苗免疫,7天后获取小鼠脾细胞,观察Poly I:C对非特异性及特异性T细胞活化的影响,并检测特异性CD8+T细胞表面PD-1表达。同时,通过敲除CD8细胞观察Poly I:C的抗肿瘤效应是否与CD8+T细胞相关。
    结果 小鼠经Poly I:C免疫后,脾组织内非特异性及特异性T细胞活化均显著增强; 活化的特异性CD8+T细胞虽高表达PD-1,但仍可合成T细胞功能性分子IFN-γ。此外,Poly I:C能显著抑制荷瘤小鼠黑色素瘤生长(P=0.0243),且该效应与CD8+T细胞有关。
    结论 Poly I:C可以促进T细胞活化; 活化早期的(脾组织内)T细胞虽高表达PD-1,但仍具有功能。

     

    Abstract:
    Objective To investigate the expression level of programmed cell death protein 1 (PD-1) in T cells at the early stage of activation (T cells remained in spleen, before migration to target organ).
    Methods C57BL/6 mice (6-8 weeks old) were immunized with Poly I:C peptide vaccine after randomly grouping. Mice spleen cells were harvested 7 days after immunization. The effects of Poly I:C on the activation of antigen specific or nonspecific T cells were evaluated. PD-1 expression on the antigen specific CD8+T cells was also detected. Furthermore, correlation between the anti-tumor effects of Poly I:C and CD8+T cells was assessed by CD8 cell knockout.
    Results Poly I:C significantly promoted the activation of antigen specific or nonspecific T cells in mice spleens. Although antigen specific T cells increased the expression of PD-1, they could still synthesize IFN-γ, a T cell functional marker. Meanwhile, Poly I:C significantly inhibited the growth of melanoma in vivo (P=0.0243), which was correlated with CD8+T cells.
    Conclusion Poly I:C could promote the activation of T cells; although, T cells at the early stage of activation (remained in spleen) enhanced the expression of PD-1, they are still functional.

     

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