Herbeuval Jean-Philippe, Shearer Gene M
UMR CNRS 8147, Hôpital Necker, Université Paris V, Paris, France.
Clin Immunol. 2007 May;123(2):121-8. doi: 10.1016/j.clim.2006.09.016. Epub 2006 Nov 16.
The hallmark of acquired immunodeficiency syndrome (AIDS) is the progressive loss of CD4+ T cells that results from infection with human immunodeficiency virus type-1 (HIV-1). Despite 25 years of AIDS research, questions remain concerning the mechanisms responsible for HIV-induced CD4+ T cell depletion. Here we briefly review the in vitro and in vivo literature concerning the protective role of interferon-alpha (IFN-alpha) in HIV/AIDS. We then develop a laboratory- and clinically supported model of CD4+ T cell apoptosis in which either infectious or noninfectious HIV-1 induces the production of type I interferon by plasmacytoid dendritic cells (pDC). The interferon produced binds to its receptor on primary CD4+ T cells resulting in membrane expression of the TNF-related apoptosis-inducing ligand (TRAIL) death molecule. The binding of infectious or noninfectious HIV-1 to CD4 on these T cells results in expression of the TRAIL death receptor 5 (DR5), leading to the selective death of HIV-exposed CD4+ T cells.
获得性免疫缺陷综合征（艾滋病）的标志是由于感染1型人类免疫缺陷病毒（HIV-1）导致CD4+ T细胞逐渐减少。尽管进行了25年的艾滋病研究，但关于HIV诱导CD4+ T细胞耗竭的机制仍存在疑问。在此，我们简要回顾关于α干扰素（IFN-α）在HIV/艾滋病中保护作用的体外和体内文献。然后，我们建立了一个得到实验室和临床支持的CD4+ T细胞凋亡模型，其中传染性或非传染性HIV-1诱导浆细胞样树突状细胞（pDC）产生I型干扰素。产生的干扰素与其在原代CD4+ T细胞上的受体结合，导致肿瘤坏死因子相关凋亡诱导配体（TRAIL）死亡分子的膜表达。传染性或非传染性HIV-1与这些T细胞上的CD4结合，导致TRAIL死亡受体5（DR5）的表达，从而导致暴露于HIV的CD4+ T细胞选择性死亡。
