Ribeiro Ruy M, Mohri Hiroshi, Ho David D, Perelson Alan S
Theoretical Division, Los Alamos National Laboratory, NM 87545, USA.
Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15572-7. doi: 10.1073/pnas.242358099. Epub 2002 Nov 14.
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.
氘代葡萄糖标记法用于测量T淋巴细胞的体内周转率。一个包含静息和活化T细胞群体的真实T细胞动力学模型，被用于拟合健康个体以及接受抗逆转录病毒治疗前后的HIV-1感染个体的d-葡萄糖标记数据。我们的分析揭示了为什么HIV-1感染会增加增殖的（Ki67(+)）CD4(+)和CD8(+) T淋巴细胞的比例，但却导致CD4而非CD8细胞耗竭。我们发现，HIV-1感染倾向于增加活化的CD4(+) T细胞的死亡和增殖速率，并增加静息CD4 T细胞活化的速率，但不会增加活化的CD4(+) T细胞的比例，这与它们在HIV-1感染个体中的优先损失相一致。相比之下，HIV-1感染不会导致活化的CD8(+) T细胞的增殖或死亡率增加，但会增加活化的CD8(+) T细胞的比例，这与这些细胞比CD4(+) T细胞在活化状态下停留更长时间并经历更多轮增殖相一致。我们的结果还解释了为什么与年龄匹配的对照组相比，HIV-1感染患者的CD8(+)细胞端粒缩短，而CD4(+)细胞端粒却没有缩短。
