Estaquier J, Monceaux V, Cumont M C, Aubertin A M, Hurtrel B, Ameisen J C
INSERM EMI 9922, Hôpital Bichat-Claude Bernard, Université Paris VII, France.
J Med Primatol. 2000 Aug;29(3-4):127-35. doi: 10.1034/j.1600-0684.2000.290305.x.
Primary infection of rhesus macaques with pathogenic strains of simian immunodeficiency virus (SIV) leads to rapid and dynamic changes in both viral load and T cell counts in the peripheral blood. We have performed a sequential analysis of peripheral blood CD4 and CD8 T cells in five macaques during the 8 weeks following SIVmac251 infection. We observed a transient lymphopenia of both CD4 and CD8 T cells during the first 2 weeks, followed by a rebound. The primary phase of infection was associated with changes in the T cells expressing CD25, CD69, or HLA-DR and with a priming of the peripheral blood CD4 and CD8 T cells for a process of apoptosis in vitro that was enhanced by CD95 (Fas) ligation, and was detected in two macaques as early as 7 days after infection. Despite the small numbers of animals studied, the importance of the early transient CD4 and CD8 T lymphopenia was positively correlated with the viral load. No correlation was found, however, between the level of activation markers expressed or of priming for apoptosis in peripheral blood T cells and the viral load. Our findings suggest the possibility that the early activation and priming for apoptosis of CD4 and CD8 T cells may involve indirect, host-related, mechanisms, or alternatively, that the T cells that remain in the peripheral blood during primary infection do not adequately reflect the viral-mediated changes in T cell activation and death that may occur in the lymphoid organs throughout the body.
用猿猴免疫缺陷病毒(SIV)的致病株对恒河猴进行初次感染,会导致外周血中病毒载量和T细胞计数迅速而动态的变化。我们对5只猕猴在感染SIVmac251后的8周内的外周血CD4和CD8 T细胞进行了连续分析。我们观察到在最初的2周内CD4和CD8 T细胞出现短暂的淋巴细胞减少,随后出现反弹。感染的初期阶段与表达CD25、CD69或HLA-DR的T细胞变化以及外周血CD4和CD8 T细胞在体外发生凋亡过程的启动有关,这种凋亡过程通过CD95(Fas)连接而增强,并且在感染后7天最早在两只猕猴中检测到。尽管研究的动物数量较少,但早期短暂的CD4和CD8 T淋巴细胞减少的重要性与病毒载量呈正相关。然而,在外周血T细胞中表达的激活标志物水平或凋亡启动水平与病毒载量之间未发现相关性。我们的研究结果表明,CD4和CD8 T细胞早期激活和凋亡启动可能涉及间接的、与宿主相关的机制,或者相反,初次感染期间留在外周血中的T细胞不能充分反映可能在全身淋巴器官中发生的病毒介导的T细胞激活和死亡变化。