Liu Jinbiao, Xiao Qianhao, Zhou Runhong, Wang Yong, Xian Qiaoyang, Ma Tongcui, Zhuang Ke, Zhou Li, Guo Deyin, Wang Xu, Ho Wen-Zhe, Li Jieliang
Animal Biosafety Level III Laboratory, Center for Animal Experiment, Wuhan University School of Basic Medical Sciences , Wuhan , China.
Department of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine , Philadelphia, PA , USA.
Front Immunol. 2016 Sep 21;7:371. doi: 10.3389/fimmu.2016.00371. eCollection 2016.
Altered T-cell homeostasis, such as expansion of CD8 T cells to the secondary lymphatic compartments, has been suggested as a mechanism of HIV/simian immunodeficiency virus (SIV)-pathogenesis. However, the role of immune activation of CD8 T cells in the CD4/CD8 turnover and viral replication in these tissues is not completely understood. In this study, we compared the expression of immune activation markers (CD69 and HLA-DR) on CD8 T cells in the peripheral blood and lymph nodes (LNs) of SIV-infected/uninfected Chinese rhesus macaques. SIV-infected macaques had significantly higher percentages of CD8CD69 and CD8HLA-DR T cells in all these anatomical compartments than uninfected macaques. LNs that located close to the gastrointestinal (GI) tract (colon, mesenteric, and iliac LNs) of SIV-infected macaques had profoundly lower numbers of CD4 T cells, but no significant difference in expression of activation marker (CD8CD69 and CD8HLA-DR) as compared with the peripheral lymphatic tissues (axillary and inguinal LNs). The CD4/CD8 ratios were negatively correlated with the activation of CD8 T cells in the overall LNs, with further associations with CD8HLA-DR in GI LNs while CD8CD69 in peripheral LNs. These observations demonstrate that the increase of CD8 T cell activation is a contributing factor for the decline of CD4/CD8 ratios in GI system.
T细胞稳态改变，如CD8 T细胞向二级淋巴器官的扩增，已被认为是HIV/猴免疫缺陷病毒（SIV）发病机制之一。然而，CD8 T细胞免疫激活在这些组织中CD4/CD8细胞更替及病毒复制中的作用尚未完全明确。在本研究中，我们比较了SIV感染/未感染的中国恒河猴外周血和淋巴结中CD8 T细胞上免疫激活标志物（CD69和HLA-DR）的表达情况。与未感染的猕猴相比，SIV感染的猕猴在所有这些解剖部位的CD8⁺CD69⁺和CD8⁺HLA-DR⁺ T细胞百分比均显著更高。SIV感染猕猴靠近胃肠道（结肠、肠系膜和髂淋巴结）的淋巴结中CD4 T细胞数量明显减少，但与外周淋巴组织（腋窝和腹股沟淋巴结）相比，激活标志物（CD8⁺CD69⁺和CD8⁺HLA-DR⁺）的表达无显著差异。在整个淋巴结中，CD4/CD8比值与CD8 T细胞的激活呈负相关，在胃肠道淋巴结中与CD8⁺HLA-DR⁺进一步相关，而在外周淋巴结中与CD8⁺CD69⁺相关。这些观察结果表明，CD8 T细胞激活增加是胃肠道系统中CD4/CD8比值下降的一个促成因素。
