Fauci A S, Schnittman S M, Poli G, Koenig S, Pantaleo G
National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Ann Intern Med. 1991 Apr 15;114(8):678-93. doi: 10.7326/0003-4819-114-8-678.
An understanding of the immunopathogenic mechanisms of infection with human immunodeficiency virus (HIV) is fundamental in developing successful approaches to designing effective therapeutic and vaccine strategies. In this regard, we have investigated the mechanisms by which HIV inserts itself into the human immune system and uses the elaborate cytokine network to its own replicative advantage. We have also shown that the burden of HIV in CD4+ T cells is directly associated with a decline in this cell population in vivo and a progression to disease. Mononuclear phagocytes may play a role in the pathogenesis of HIV infection by serving as reservoirs of the virus. Of note is the fact that monocytes in the peripheral blood of HIV-infected individuals are rarely infected in vivo, whereas infected-tissue macrophages may play a role in organ-specific HIV-related pathogenesis. The role of HIV-specific humoral and cell-mediated immunity in HIV infection is not well understood. However, fine specificity of responses against HIV have been delineated in some in-vitro systems. It is unclear why these responses, particularly HIV-specific cytolytic T-cell responses, diminish over the course of infection and are unable to contain progression of infection.
了解人类免疫缺陷病毒(HIV)感染的免疫致病机制是开发成功的有效治疗和疫苗策略设计方法的基础。在这方面,我们研究了HIV插入人体免疫系统并利用复杂的细胞因子网络获得自身复制优势的机制。我们还表明,CD4+T细胞中的HIV负担与体内该细胞群体的减少以及疾病进展直接相关。单核吞噬细胞可能作为病毒储存库在HIV感染的发病机制中发挥作用。值得注意的是,HIV感染个体外周血中的单核细胞在体内很少被感染,而受感染组织中的巨噬细胞可能在器官特异性HIV相关发病机制中起作用。HIV特异性体液免疫和细胞介导免疫在HIV感染中的作用尚未完全了解。然而,在一些体外系统中已经明确了针对HIV的反应的精细特异性。目前尚不清楚为什么这些反应,特别是HIV特异性细胞毒性T细胞反应,在感染过程中会减弱,并且无法遏制感染的进展。