Beaulieu S, Kessous A, Landry D, Montplaisir S, Bergeron D, Cohen E A
Départment de microbiologie et immunologie, Faculté de médecine, Université de Montréal, Québec, Canada.
Virology. 1996 Aug 1;222(1):214-26. doi: 10.1006/viro.1996.0412.
In the thymus, dendritic cells (DC) are functionally associated with thymocytes and are recognized to play a major role in the intrathymic differentiation of T cells. Several studies have previously investigated the role of DC during HIV-infection, but the status of thymic DC in HIV-1 pathogenesis remains unclear. In this study, we investigated the susceptibility of purified human thymic DC to HIV-1 infection in vitro. HIV-1 was not detected in cell-free supernatants collected from HIV-infected DC. However, these cultures were shown to transmit HIV-1 infection since coculture with permissive MT4 cells resulted in virus production. The exposure of DC in culture to HIV-1 was shown to promote severe DC morphological changes and killing. We also found that one or several heat labile soluble cytotoxic agents present in the HIV-1-infected DC supernatant mediated the killing of thymocytes. Our observations raise the possibility that (1) the HIV-1-induced DC killing, (2) the capacity of DC to transmit viral infection, and/or (3) the release of HIV-1-mediated cytotoxic agent(s) from DC may contribute to AIDS pathogenesis in vivo.
在胸腺中,树突状细胞(DC)在功能上与胸腺细胞相关联,并且被认为在T细胞的胸腺内分化中起主要作用。此前已有多项研究探讨了DC在HIV感染过程中的作用,但胸腺DC在HIV-1发病机制中的状态仍不清楚。在本研究中,我们在体外研究了纯化的人胸腺DC对HIV-1感染的易感性。从感染HIV的DC收集的无细胞上清液中未检测到HIV-1。然而,这些培养物被证明可传播HIV-1感染,因为与易感的MT4细胞共培养会导致病毒产生。培养中的DC暴露于HIV-1会导致严重的DC形态变化和死亡。我们还发现,HIV-1感染的DC上清液中存在一种或几种热不稳定的可溶性细胞毒性因子介导了胸腺细胞的死亡。我们的观察结果提出了以下可能性:(1)HIV-1诱导的DC死亡,(2)DC传播病毒感染的能力,和/或(3)DC释放HIV-1介导的细胞毒性因子可能在体内导致艾滋病发病机制。