Effects of IL-7 on early human thymocyte progenitor cells in vitro and in SCID-hu Thy/Liv mice
Effects of IL-7 on early human thymocyte progenitor cells in vitro and in SCID-hu Thy/Liv mice
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DOI：
10.4049/jimmunol.171.2.645
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发表时间：
2003-07-15
影响因子：
4.4
通讯作者：
McCune, JM
中科院分区：
文献类型：
--
作者：
Napolitano, LA;Stoddart, CA;McCune, JM
IL-7是动物胸腺生成的重要组成部分，最近被证明在T细胞稳态中起重要作用。尽管人们对使用IL-7治疗由1型HIV引起的淋巴细胞减少症越来越感兴趣，但IL-7可能加速HIV复制的证据引起了人们对其在这种情况下使用的担忧。我们试图确定IL-7对人胸腺细胞存活的影响，并确定IL-7给药对人胸腺体内HIV感染的影响。通过体外分析，我们发现IL-7为早期胸腺细胞祖细胞提供了有效的抗凋亡和增殖信号。对CD34（+）亚群的分析表明，表面IL-7受体在大多数CD34（高）CD5(+)CD1a（-）胸腺细胞上表达，并且该亚群似乎是响应IL-7作用的最早成熟阶段之一。因此，在CD1a表面表达之前，IL-7向人胸腺细胞提供了存活信号。CD4(+)CD8（+）胸腺细胞对IL-7相对无反应，尽管IL-7保护这些细胞免受地塞米松诱导的凋亡。IL-7对成熟的CD4(+)CD3(+)CD8（-）和CD8(+)CD3(+)CD4（-）胸腺细胞具有主要的增殖作用。与体外研究结果相反，我们观察到，在体内给SCID-hu Thy/Liv小鼠注射IL-7似乎不会增强胸腺细胞存活，也不会加速HIV感染。鉴于人们对使用IL-7治疗人类免疫缺陷的兴趣日益浓厚，这些发现支持进一步研究其对胸腺增生和HIV感染的体内影响。
IL-7 is a critical component of thymopoiesis in animals and has recently been shown to play an important role in T cell homeostasis. Although there is increasing interest in the use of IL-7 for the treatment of lymphopenia caused by the HIV type 1, evidence that IL-7 may accelerate HIV replication has raised concerns regarding its use in this setting. We sought to identify the effects of IL-7 on human thymocyte survival and to determine the impact of IL-7 administration on in vivo HIV infection of the human thymus. Using in vitro analysis, we show that IL-7 provides potent anti-apoptotic and proliferative signals to early thymocyte progenitors. Analysis of CD34(+) subpopulations demonstrates that surface IL-7 receptor is expressed on most CD34(high) CD5(+)CD1a(-) thymocytes and that this subpopulation appears to be one of the earliest maturation stages responsive to the effects of IL-7. Thus, IL-7 provides survival signals to human thymocytes before surface expression of CD1a. CD4(+)CD8(+) thymocytes are relatively unresponsive to IL-7, although IL-7 protects these cells from dexamethasone-induced apoptosis. IL-7 has a predominantly proliferative effect on mature CD4(+)CD3(+)CD8(-) and CD8(+)CD3(+)CD4(-) thymocytes. In contrast to the in vitro findings, we observe that in vivo administration of IL-7 to SCID-hu Thy/Liv mice does not appear to enhance thymocyte survival nor does it appear to accelerate HIV infection. Given the growing interest in the use of IL-7 for the treatment of human immunodeficiency, these findings support additional investigation into its in vivo effects on thymopoiesis and HIV infection.