泰素对调节性和效应性T细胞不同作用的机制研究Possible.PPTVIP

* 有趣的是，实验室前期研究发现，在NSCLC患者中，应用… * * 那大家要问了，Treg和Teff细胞在免疫系统中扮演着怎样的角色呢？ * ……因此，抑制Treg细胞而保护Teff细胞对于抗肿瘤免疫是至关重要的，而PTX对免疫系统的作用正符合了这一要求。 * Then, why would PTX have different effects on two T cell subsets? What’s the mechanism behind it? That’s the focus of my research. 这一机理的探索可能为化疗药将来更安全有效地使用提供理论基础。 * * TLR4是一类细胞表面分子，是细胞对外界信号的接收器，广泛参与了各种细胞活动的调控。有研究发现，PTX可以激活固有免疫细胞表面的TLR4，从而参与固有免疫应答，那么PTX是否也可以激活Treg上的TLR4呢，它对两群细胞的不同作用是否与TLR4相关呢？ * On both mRNA and protein level, TLR4 expression on Treg cells is higher than that on Teff cells. * Further more, we sorted Treg and Teff cells to detect possible changes of TLR4 and surface molecules after PTX treatment. However, TLR4 expression didn’t change after PTX treatment in both Treg and Teff cells. Neither did costimulator markers or activation markers. Those results indicated that TLR4 may not be involved in the different effect of PTX. In order to confirm the results，we repeated the experiments on TLR4-/- mice which is deficient in TLR4 signal pathway. TLR4-/- mice responded similarly with wild type, in terms of Treg percentage, cell viability, and cytokine production. It turns out that TLR4 is not the reason for the different effect of PTX. We need to explore the mechanism further. * * PTX directly targets Bcl-2 in the loop domain, thereby facilitating the initiation of apoptosis. Is it possible that apoptosis induced by Bcl-2/Bax regulation plays a role here? * A significant increase in apoptosis of Treg cells after PTX treatment was observed, while the apoptosis of Teff cells didn’t change. * By Western Blot analysis, we could see the Bcl-2 expression on Treg cells decreased in a dose-dependent way after PTX treatment. And Bax expression on Treg cells increased correspondingly. While both Bcl-2 and Bax expression on Teff cells didn’t change after PTX treatment. What’s more, the Bcl-2 inhibitor ABT 737 abolished the difference in cell viability of Treg cells after PTX treatment. It further confirmed the role of Bcl-2 in the effect