文章基本信息

标题：In vivo dynamics of T cell activation, proliferation, and death in HIV-1 infection: Why are CD4+ but not CD8+ T cells depleted?
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作者：Ruy M. Ribeiro ; Hiroshi Mohri ; David D. Ho 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：24
页码：15572-15577
DOI：10.1073/pnas.242358099
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Deuterated glucose labeling was used to measure the in vivo turnover of T lymphocytes. A realistic T cell kinetic model, with populations of resting and activated T cells, was fitted to D-glucose labeling data from healthy and HIV-1-infected individuals before and after antiretroviral treatment. Our analysis highlights why HIV-1 infection, which increases the fraction of both CD4+ and CD8+ T lymphocytes that are proliferating (Ki67+), leads to CD4 but not CD8 depletion. We find that HIV-1 infection tends to increase the rates of death and proliferation of activated CD4+ T cells, and to increase the rate at which resting CD4 T cells become activated, but does not increase the fraction of activated CD4+ T cells, consistent with their preferential loss in HIV-1-infected individuals. In contrast, HIV-1 infection does not lead to an increase in proliferation or death rates of activated CD8+ T cells, but did increase the fraction of activated CD8+ T cells, consistent with these cells remaining in an activated state longer and undergoing more rounds of proliferation than CD4+ T cells. Our results also explain why telomeres shorten in CD8+ cells, but not in CD4+ cells of HIV-1-infected patients, compared with age-matched controls.