中医药对HIV感染ⅡA期特异性CTL应答调节及其机制探索

By adjusting the immune systems of the body, traditional Chinese medicine (TCM) can be used to treat Stage ⅡA HIV infection and delayed the progression of HIV/AIDS. At this stage, HIV-specific cytolytic T lymphocytes (CTL) are closely related with the advancement of HIV/AIDS. Researches should be conducted to study whether the improvement of immune system caused by TCM is related with the fact that TCM can adjust the immune response of HIV-specific CTL. At the present study, multi-layered methods (cellular and molecular methods) and various measures (eg. live cell fluorescence in situ imaging, flow cytometry, molecular biological measures) were used to compare the difference between the patients treated with and without TCM regarding the number of peripheral T lymphocyte subsets, plasma cytokine level, peripheral blood mononuclear cells (PBMCs), surface markers of different types of T cells, the changes of CD8 T cells cytokine level and programmed cell death, and to analyze whether the differences were related with the response of HIV-specific CTL. The influences of TCM on immune response of HIV-specific CTL were studied. The mechanisms how TCM could improve the immune system of patient with Stage ⅡA HIV infection and stop or delay the advance of Stage ⅡA HIV infection to Stage ⅡB or Stage Ⅲ HIV infection were explored, which can supply scientific evidence and support for the use of TCM in HIV mid-term infection treatment.

中医药可在HIV感染ⅡA期介入治疗，通过调节机体免疫功能延缓艾滋病进程，而此期HIV特异性CTL应答与艾滋病进展密切相关，应对中医药在此期改善机体免疫状况的效果是否与调节感染者的HIV特异性CTL应答有关进行探索。本项研究采用多层次（细胞，分子）和多手段（原位活细胞荧光成像技术，流式细胞分析术，分子生物学等）相结合的方法，比较分析HIV感染IIA期中医药治疗/未治疗的患者外周血T淋巴细胞亚群数量、血浆细胞因子含量、PBMCs不同T淋巴细胞表面标记、CD8+T细胞内细胞因子分泌及其细胞凋亡的动态变化与感染者的HIV特异性CTL反应的关系，分析中医药对机体HIV特异性CTL应答调节的影响，探讨中医药提高HIV感染IIA期患者机体免疫功能阻止或延缓向ⅡB和Ⅲ期过渡的机制，为临床广泛开展HIV感染中期中医药治疗提供科学依据和支持。

近30年来众多中医药工作者对艾滋病的临床治疗进行了有意义的探索，研究提示中医药从整体调节角度入手，对人体免疫功能具有独特的调节作用。临床上针对IIA期患者一般采用单纯中医药治疗，应用实践表明中医药在此期干预治疗，可保护和提高感染者的免疫功能，但其作用机制尚未阐释清楚。本研究应用现代免疫学研究技术和手段从细胞和分子水平来探索中医药治疗对HIV感染者CTL应答的作用及其机制。通过对自然病程和中医药治疗的HIV感染IIA期患者为期18个月的临床治疗观察，分析治疗前后二组患者HIV特异性CTL反应、T细胞亚群数量、相关的细胞表面标记、细胞因子的变化，结果提示中医药治疗可以改善患者临床症状体征，稳定和维持CD3+CD4+T淋巴细胞亚群，增强HIV特异性CTL应答。中医药治疗组患者的CD8+T淋巴细胞上共刺激分子CD28表达上升，CD8+CD28-T淋巴细胞亚群比例维持稳定；CD4+T淋巴细胞上CD95分子表达维持稳定，而CD8+T淋巴细胞上CD95分子表达随着治疗时间的推延而下降；外周血细胞因子IFN-γ、TNF-a、IL-2、IL-4、IL-12和穿孔素水平明显上升，上升程度不一。而自然病程组随着治疗时间的推移，HIV特异性CTL应答减弱，CD8+T淋巴细胞上共刺激分子CD28表达无明显变化；CD8+T淋巴细胞上CD95分子表达随着时间的推延而上升；外周血细胞因子IFN-γ、TNF-a、IL-12维持稳定，IL-4上升，IL-2和穿孔素下降。中医药治疗艾滋病有其独特的优势，但其作用及其机制未阐释清楚一直制约其临床推广应用，本研究结果提示中医药早期介入治疗可以通过增强CTL应答来提高机体免疫功能，增强自身的抗病毒能力，进而延缓艾滋病进程，为临床广泛开展HIV感染中医药治疗提供科学依据和支持。