Subpopulations of long-lived and short-lived T cells in advanced HIV-1 infection
Subpopulations of long-lived and short-lived T cells in advanced HIV-1 infection
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DOI：
10.1172/jci200317533
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发表时间：
2003-09-01
影响因子：
15.9
通讯作者：
McCune, JM
中科院分区：
文献类型：
--
作者：
Hellerstein, MK;Hoh, RA;McCune, JM
抗原刺激T细胞产生短期效应细胞和长期记忆细胞。我们使用了两种稳定的同位素标记技术来鉴定动力学上不同的T细胞亚群，并确定HIV-1晚期感染的影响。长期将氘化水(H2O)-H-2掺入DNA中表明，总表型和记忆/效应（m/e）型T细胞呈双相累积，而非初始表型T细胞，这与m/e表型T细胞池中存在短寿和长寿亚群相一致。这些结果反映在短期h -2-葡萄糖标记后m/e-而非naive-表型T细胞的双相死亡动力学中。在m/e表型T细胞（可能是记忆T细胞）的一个子集中观察到持久的标签保留，证实了人类中存在具有非常不同寿命的T细胞。在晚期HIV-1感染中，与健康对照组相比，T细胞的短命率要高得多。长期有效的抗逆转录病毒治疗使其恢复正常。这些结果提供了第一个定量证据，证明长寿命和静止的T细胞确实在人类的T细胞池中占主导地位，并决定了T细胞池的大小，就像在啮齿动物中一样。晚期HIV-1感染的最大影响是减少长寿命的潜在祖T细胞的产生。
Antigenic stimulation of T cells gives rise to short-lived effector cells and long-lived memory cells. We used two stable isotope-labeling techniques to identify kinetically distinct subpopulations of T cells and to determine the effect of advanced infection with HIV-1. Long-term deuterated water ((H2O)-H-2) incorporation into DNA demonstrated biphasic accrual of total and of memory/effector (m/e)-phenotype but not naive-phenotype T cells, consistent with the presence of short-lived and longer-lived subpopulations within the m/e-phenotype T cell pool. These results were mirrored by biphasic die-away kinetics in m/e- but not naive-phenotype T cells after short-term H-2-glucose labeling. Persistent label retention was observed in a subset of m/e-phenotype T cells (presumably memory T cells), confirming the presence of T cells with very different life spans in humans. In advanced HIV-1 infection, much higher proportions of T cells were short-lived, compared to healthy controls. Effective long-term anti-retroviral therapy restored values to normal. These results provide the first quantitative evidence that long-lived and quiescent T cells do indeed predominate in the T cell pool in humans and determine T cell pool size, as in rodents. The greatest impact of advanced HIV-1 infection is to reduce the generation of long-lived, potential progenitor T cells.