Bremermann H J
Department of Molecular and Cell Biology, University of California, Berkeley, USA.
J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Aug 15;9(5):459-83.
Periodic infusion of autologous HIV-antigen presenting cells (APCs), that stimulate the cytotoxic (CTL) response, while being incapable of producing virus, should lower viral burden and boost CD4+ count in HIV-seropositive individuals. Viral burden reasserts itself after antiviral therapy ceases or is interrupted for long. Therapy, therefore, would have to continue for life. These are predictions from a computer model of HIV-immune kinetics. The model equations describe the interactive kinetics of viral burden, CD4+ cell decline, neutralization of free virus by antibodies, infection of cells, and killing of infected cells by CTL. The computed trajectories of the kinetic equations reproduce the typical course of an HIV infection and the model yields several predictions that are not intuitively obvious, among them: (a) Persistence of HIV infection (failure of the immune system to clear infection) is an intrinsic property of the kinetics of the HIV-immune interaction. (b) The chronic state of infection is inherently stable, which means that the infection rebounds to the determined steady state, whenever antiviral therapy stops. (c) CTL is chronically activated, and the level correlates inversely with the avidity of neutralizing antibodies. (d) APCs have to be infused at a rate such as to boost and maintain the CTL response above the chronic level. Other therapies include CTL stimulation, via the macrophage route, by erythrocytes, into which MHC binding HIV-CTL epitope polypeptide fragments have been inserted; passive immunization, virion-trapping by CD4 analogs or CD4 expressing erythrocytes; and combination therapies with AZT, IL-2. These are also analyzed. Concerning HIV etiology, the model assumes that cells other than CD4+ cells (such as macrophages/monocytes) become infected, and contribute to the viral burden, and that infectible cells remain available even as CD4+ cells become exhausted. The model further assumes that CD4+ cells decline not only through direct killing by HIV and CTL, but by dysregulation and excess apoptosis caused by the presence of virus. The model predicts that persistence of HIV infection does not depend upon latently infected cells or escape mutants, as has been suggested.(ABSTRACT TRUNCATED AT 400 WORDS)
定期输注自体HIV抗原呈递细胞（APC），这种细胞能刺激细胞毒性（CTL）反应，同时又无法产生病毒，应该能够降低HIV血清阳性个体的病毒载量并提高CD4 +细胞计数。在抗病毒治疗停止或长期中断后，病毒载量会再次出现。因此，治疗将不得不持续终身。这些是来自HIV免疫动力学计算机模型的预测。该模型方程描述了病毒载量、CD4 +细胞下降、抗体对游离病毒的中和、细胞感染以及CTL对感染细胞的杀伤的相互作用动力学。动力学方程的计算轨迹再现了HIV感染的典型病程，并且该模型产生了几个并非直观明显的预测，其中包括：（a）HIV感染的持续存在（免疫系统清除感染失败）是HIV -免疫相互作用动力学的固有特性。（b）感染的慢性状态本质上是稳定的，这意味着每当抗病毒治疗停止时，感染会反弹至确定的稳态。（c）CTL长期被激活，其水平与中和抗体的亲和力呈负相关。（d）必须以一定速率输注APC，以提高并维持CTL反应高于慢性水平。其他疗法包括通过巨噬细胞途径，利用插入了结合HIV - CTL表位多肽片段的MHC的红细胞来刺激CTL；被动免疫，用CD4类似物或表达CD4的红细胞捕获病毒粒子；以及与AZT、IL - 2的联合疗法。这些也进行了分析。关于HIV病因，该模型假设除CD4 +细胞外的其他细胞（如巨噬细胞/单核细胞）会被感染，并导致病毒载量增加，并且即使CD4 +细胞耗尽，可感染细胞仍然存在。该模型还假设CD4 +细胞的下降不仅通过HIV和CTL的直接杀伤，还通过病毒存在导致的失调和过度凋亡。该模型预测，HIV感染的持续存在并不取决于潜伏感染细胞或逃逸突变体，正如有人所提出的那样。（摘要截断于400字）
