猴艾滋病模型急性感染期的T细胞各亚群变化规律研究

Research on change of T cell subsets in acute phase of SIV/SAIDS

目的探索猴艾滋病模型急性感染期T细胞各亚群动态变化规律。方法 15只健康恒河猴经静脉注射SIVmac239病毒株,建立猴艾滋病模型。分别在感染前、感染后一个月和感染后两个月检测T细胞功能亚群、纯真亚群和记忆亚群以及血常规和血生化指标;在感染后半个月、一个月、两个月、两个半月采集外周血检测血浆病毒载量,然后比较各个时间点间各指标的变化情况。结果感染半月时病毒载量最高,与感染一月、感染两月、感染两个半月3个时间点间有明显差异,而此3个时间点间病毒拷贝无明显差异;T细胞各亚群百分比与个数变化基本一致;CD4+CD28-T细胞与CD8+CD28+T细胞(杀伤性T细胞)感染前后变化不明显,而CD4+CD28+T细胞相比感染前显著下降(P<0.01),CD8+CD28-T细胞(抑制性T细胞)相比感染前显著升高(P<0.01),推测机体可能通过抑制性T细胞的大量增加来加强抑制CD4+T细胞增殖活化的作用,从而减少CD4+T细胞感染SIV;CD4纯真细胞在急性感染期先下降后回升,而CD4记忆细胞感染后呈下降趋势,未出现回升,变化趋势与CD4+T细胞一致,说明在急性感染期中减少的CD4+T细胞以记忆性CD4+T细胞为主。结论在急性感染期CD4+T细胞数量发生改变,减少的CD4+T细胞以记忆性CD4+T细胞为主,同时CD4+T细胞的功能也受到影响;推测机体可能启动了一种被动的保护机制:大量增加抑制性T细胞来加强抑制CD4+T细胞的增殖活化,从而间接减少CD4+T细胞感染SIV。

This study designed to explore the dynamic change rule of T cell subsets in acute phase of SIW SAIDS. Total of 15 healthy rhesus monkeys were selected to build simian immunodeficiency virus （SIV） model of acquired immune deficiency syndrome （AIDS） with intravenous infection of SIVmac239. Then the functional subsets, naive subsets, memory subsets of T cell were detected, and blood test, liver function test, renal function test were performed before infection, one month and two months post infection; peripheral blood viral load was tested in half of a month, one month , two months, and two and a half months post infection. We found that the peripheral blood viral load was the highest in a half months post infection, compared with that of one month, two months and two and a half months post infection, but there was no difference among the three time points. For T cell subsets, their percentage change was in accordance with their count change. In detail, CD4＋CD28-T cell and CD8＋CD28＋T cell （cytotoxic T cell） did not changed much after infection; while CD4＋CD28＋T cell declined significantly （P〈 0.01）, CD8＋CD28-T cell （suppressor T cell） raised significantly （P〈 0.01）, which implied that the body may produce more suppressor T cell to strengthen the inhibition on CD4＋T cell proliferation, thus reduce the CD4CF cells infected with SIV. CD4 naive cell felled at first, then raised again later in acute phase, but CD4 memory cell did not rise again after declining, which was similar to the change of CD4＋T cell, suggesting that the decreased CD4＋T cells is mainly memory CD4＋T cells in acute phase. In conclusion, the count of CD4＋ cell changes in acute phase, and the decreased CD4Cr cells is mainly memory CD4＋cells. The function of CD4＋T cell is in cumbered at the same time. All these change suggested that body maybe start a kind of passive protection mechanism： strengthening inhibition of CD4＋T cell proliferation by dint of a large increase of suppressor T cell, thus reducing the CD4＋T cells infectedwith SIV indirectly.