T-cell homeostasis, competition, and drift: AIDS as HIV-accelerated senescence of the immune repertoire.
T-cell homeostasis, competition, and drift: AIDS as HIV-accelerated senescence of the immune repertoire.
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T 细胞稳态、竞争和漂移：艾滋病是艾滋病毒加速的免疫系统衰老。
DOI：
10.1097/00042560-199607000-00003
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Antia,R
中科院分区：
文献类型：
--
作者：
Mittler,JE;Levin,BR;Antia,R
成年 HIV-1/AIDS 患者中 CD8+ T 淋巴细胞密度随着 CD4+ T 细胞密度下降而增加，加上 T 细胞总密度受到调节（稳态）的证据，表明 T 细胞谱系和类别之间的竞争有助于 HIV 的病理学。我们使用 T 细胞群、HIV 和其他寄生虫之间相互作用的数学模型来探索 T 细胞稳态和竞争对艾滋病进展的影响。我们证明，由于寄生虫介导的 T 细胞复制、不同 T 细胞克隆内部和之间的竞争以及随机过程（T 细胞漂移），一些 CD4+ 谱系将由相对较少的细胞代表，导致细胞缺失，并且一些谱系可能会丢失，从而在免疫库中留下漏洞。通过杀死 CD4+ T 淋巴细胞，HIV 加速了这些缺失和空洞积累的速度，并导致 HIV 和其他寄生虫（艾滋病）的免疫控制早期崩溃。当该模型考虑到 CD4+ 和 CD8+ T 细胞群之间激烈但不完全的竞争时，它可以解释成人 HIV-1 感染的大部分特征，包括 CD4+ T 细胞密度逐渐下降和 HIV 密度随之增加，以及老年患者从感染到艾滋病的时间变异和从感染到艾滋病的时间缩短。
The observation that the density of CD8+ T-lymphocytes increases as the density of CD4+ T-cells declines in adult HIV-1/AIDS patients, together with evidence that the total density of T-cells is regulated (homeostasis) has led to the suggestion that competition between lineages and classes of T-cells contributes to the pathology of HIV. We use a mathematical model of the interactions between populations of T-cells, HIV, and other parasites to explore the effects of T-cell homeostasis and competition on the progression to AIDS. We demonstrate that as a consequence of parasite-mediated T-cell replication, of competition within and between different T-cell clones, and random processes (T-cell drift), some CD4+ lineages will be represented by relatively few cells, dearths, and some lineages may be lost, leaving holes in the immune repertoire. By killing CD4+ T-lymphocytes, HIV accelerates the rate at which these dearths and holes accumulate and leads to an early breakdown of the immune control of HIV and other parasites, AIDS. When this model allows for intense, but not complete, competition between the CD4+ and CD8+ T-cell populations, it can account for most of the features of an HIV-1 infection in adults, including the gradual decline in CD4+ T-cell densities and concomitant increase in HIV density, as well as the variability in time from infection to AIDS and the decline in the time from infection to AIDS in older patients.