Kirschner D, Webb G F, Cloyd M
Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, Michigan, USA.
J Acquir Immune Defic Syndr. 2000 Aug 1;24(4):352-62. doi: 10.1097/00126334-200008010-00010.
Several proposed theories have described the progression of HIV infection. Even so, no concrete evidence supports any as comprehensive, including, for example, why the CD4+ T-cell counts fall from 1000/mm3 of blood to roughly 100/mm3 over an average 10-year period, whereas concomitant viral loads are relatively constant, increasing by several orders of magnitude in late-stage disease. Here, we develop and validate a theoretical model that altered lymphocyte circulation patterns between the lymph system and blood due to HIV-induced enhanced lymph-node homing and subsequent apoptosis of resting CD4+ T cells can explain many aspects of HIV-1 disease progression. These results lead to a recalculation of the CD4+ lymphocyte dynamics during highly active antiretroviral therapy, and also suggest new targets for therapy.
已有几种提出的理论描述了HIV感染的进展过程。即便如此，尚无确凿证据支持任何一种理论具有全面性，例如，为何在平均10年的时间里，血液中CD4+ T细胞计数从每立方毫米1000个降至约每立方毫米100个，而同时病毒载量相对恒定，在疾病晚期增加几个数量级。在此，我们构建并验证了一个理论模型，该模型表明，由于HIV诱导的淋巴结归巢增强以及静息CD4+ T细胞随后的凋亡，导致淋巴细胞在淋巴系统和血液之间的循环模式发生改变，这可以解释HIV-1疾病进展的许多方面。这些结果导致了在高效抗逆转录病毒治疗期间对CD4+淋巴细胞动力学的重新计算，也提示了新的治疗靶点。
