灭活自体T细胞增强小鼠免疫功能作用机制的研究

Study on enhanced immune response by immunization with attenuated activated autologous T cells

接种灭活自身反应性T细胞用于治疗自身免疫性疾病已获初步成效。本研究采用辐射方法灭活ConA活化自体T细胞,经皮下和腹腔免疫正常的C57BL/6J小鼠,结果发现,该免疫方案可明显上调T细胞功能,表现为:免疫小鼠体内活化T细胞增多且Th1型细胞因子分泌增加,淋巴细胞体外增殖能力增强且凋亡细胞明显减少。进一步研究结果提示,接种灭活自体T细胞可能通过上调Fas、GADD45β及下调FasL基因表达而促进T细胞的活化和存活,并增加其生物学功能。这些结果表明,自体T细胞免疫具有增强机体的细胞免疫功能,为其抗肿瘤免疫作用提供了一定的实验依据。

Immunization with inactivated autoreactive T cells （T cell vaccination） was used as potential therapy for the patients with various autoimmune diseases. To explore whether attenuated ConA （concanavalin A） activated autologous T cell immuni- zation could increase T cell functions, C57BL/6J mice were immunized with these attenuated autologous T cell by intraperitoneal and subcutaneously injection. T cells from the immunized mice showed increased expression of T cell activation markers and enhanced proliferation in response to ConA. Moreover, Levels of IFN-γ, IL- 12 and TNF-α were increased in the sera of immunized mice. These results demonstrated that this immunization might activate T cells in vivo. Furthermore, the splenocytes from immunized mice revealed resistance to activation induced cell death （AICD） in vitro. To further study the relative genes that responsible for the higher proliferation and resistance to AICD, the expression of Fas, FasL and GADD4513 was measured by real-time PCR. The results indicated that GADD45β and Fas expression was higher in the splenocytes from immunized mice than that from control mice, whereas FasL expression was lower than control mice. This study implicated that im- munization with attenuated ConA activated autologous T cells enhances T cells function with potential contribution to tumor growth inhibition.