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目的研究B亚型强毒株SHIVSF162p3感染恒河猴后,在感染慢性期肠道组织、外周血及淋巴结中T淋巴细胞亚群的频率及其与急性期病毒复制强度的相关性。方法使用SHIVSF162p3通过静脉及黏膜途径感染12只中国恒河猴,real-time RT-PCR监测血浆病毒载量。感染慢性期取外周血、淋巴结以及通过内窥镜手术取十二指肠肠道黏膜组织,分离淋巴细胞,使用多色流式细胞术检测分析各组织中CD4+T细胞各亚群频率。结果与健康猴相比,SHIVSF162p3感染慢性期3种淋巴组织中CD4+T均有所下降且减少的主要部分是Tcm亚群,而CD4+Tcm下降在肠道组织中最为显著。与CD4+T细胞比较,慢性期CD4+Tcm的下降与急性期病毒载量峰值的相关性更高。从组织学来看,慢性期肠道组织CD4+Tcm与病毒载量峰值相关性最高,外周血次之;淋巴结的关联性不大。结论 B亚型强毒株SHIVSF162p3在急性感染期首先攻击肠道组织和外周血中CD4+Tcm细胞,造成靶细胞的严重损毁。病毒复制率越高损毁越严重,且持续至病毒感染慢性期,可能是这两种淋巴组织中CD4+T细胞下降的主要原因。而淋巴结中CD4+Tcm的下降则主要与外周血和淋巴结间的淋巴细胞循环相关。
Objective To study the frequency of T lymphocyte subsets and its relationship with acute viral replication in chronic phase of intestine infection, peripheral blood and lymph nodes after infected with SHIVSF162p3. Methods SHIVSF162p3 was used to infect 12 Chinese rhesus monkeys by intravenous and mucosal routes. The plasma viral load was monitored by real-time RT-PCR. Peripheral blood and lymph nodes were collected during chronic infection, and the intestinal mucosa of duodenum was removed by endoscopic surgery. Lymphocytes were isolated and the subsets of CD4 + T cells in each tissue were analyzed by multi-color flow cytometry. Results Compared with healthy monkeys, the percentage of CD4 + T in the three chronic lymphatic tissues infected with SHIVSF162p3 was significantly lower than that in healthy monkeys. The decrease in CD4 + Tcm was the most significant in intestinal tissues. Compared with CD4 + T cells, the decrease of CD4 + Tcm in chronic phase was more correlated with the peak of acute viral load. From the histological point of view, chronic intestinal phase CD4 + Tcm peak correlation with the highest viral load, followed by peripheral blood lymph nodes is not associated. Conclusion SHIVSF162p3, a subtype B virulent strain, first attacked CD4 + Tcm cells in intestinal tissue and peripheral blood during acute infection, resulting in severe damage of target cells. The higher the virus replication rate, the more serious the damage, and continues to the chronic phase of virus infection, which may be the main reason for the decline of CD4 + T cells in both lymphoid tissues. However, the decrease of CD4 + Tcm in lymph nodes was mainly related to the lymphocytic circulation between peripheral blood and lymph nodes.