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  • 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?
  • 本地全文:下载
  • 作者:Ruy M. Ribeiro ; Hiroshi Mohri ; David D. Ho
  • 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.
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