CD127 expression and regulation are altered in the memory CD8 T cells of HIV-infected patients -: reversal by highly active anti-retroviral therapy (HAART)
CD127 expression and regulation are altered in the memory CD8 T cells of HIV-infected patients -: reversal by highly active anti-retroviral therapy (HAART)
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DOI：
10.1111/j.1365-2249.2006.03022.x
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发表时间：
2006-03-01
影响因子：
4.6
通讯作者：
Thèze, J
中科院分区：
文献类型：
--
作者：
Colle, JH;Moreau, JL;Thèze, J
HIV感染会异常激活免疫系统，慢性期伴随着CD8细胞的显著变化。本文分析和报道了HIV感染者记忆性CD8 T淋巴细胞CD127(IL-7Rα链)的表达。用CD45RA和CD27标记检测CD8T细胞亚群的表达，四色流式细胞术检测CD127细胞表面的表达。HIV感染与CD127(+)细胞在记忆性CD8淋巴细胞中的比例下降有关，这导致HIV感染者CD127(-)CD45RA(-)CD27(+)CD8 T细胞计数升高。在这个亚群中，阳性细胞的CD127细胞表面表达降低[平均荧光强度(MFI)]。这些数据表明，这些缺陷可以通过高效抗逆转录病毒疗法(HAART)得到逆转。体外实验还研究了CD127的表达调控。在正常人和HAART患者的记忆性CD8淋巴细胞中观察到IL-7对CD127的下调作用。在无IL-7条件下培养的记忆性CD8淋巴细胞表达CD127证实了病毒感染患者IL-7R调节的改变。在相同的实验条件下，来自HAART患者的记忆CD8淋巴细胞表达CD127的水平与来自健康人的细胞相当。HIV感染者记忆性CD8 T淋巴细胞表面CD127表达改变和CD127调节缺陷可能是这些细胞对内源性IL-7刺激信号的生理反应受阻的潜在机制。我们的数据表明，在HAART之后的免疫重建过程中，这些缺陷被逆转。
HIV infection activates abnormally the immune system and the chronic phase is accompanied by marked alterations in the CD8 compartment. The expression of CD127 (IL-7R alpha chain) by memory CD8 T lymphocytes in HIV-infected patients is analysed and reported. The memory CD8 T cell subset was characterized by expression of CD45RA and CD27 markers, and CD127 cell surface expression was measured ex vivo by four-colour flow cytometry. HIV infection was associated with a fall in the proportion of CD127(+) cells among memory CD8 lymphocytes that resulted in a higher CD127(-) CD45RA(-)CD27(+) CD8 T cell count in HIV-infected patients. Diminished CD127 cell surface expression [mean fluorescence intensity (MFI)] by positive cells was also observed in this subset. The data suggest that these defects were reversed by highly active anti-retroviral therapy (HAART). The regulation of CD127 expression was also studied in vitro. Down-regulation of CD127 by interkeukin (IL)-7 was observed in memory CD8 lymphocytes from healthy donors and HAART patients. Expression of CD127 by memory CD8 lymphocytes cultured in the absence of IL-7 confirmed that IL-7R regulation is altered in viraemic patients. Under the same experimental conditions, memory CD8 lymphocytes from HAART patients were shown to express CD127 at levels comparable to cells from healthy individuals. Altered CD127 cell surface expression and defective CD127 regulation in the memory CD8 T lymphocytes of HIV-infected patients are potential mechanisms by which these cells may be impeded in their physiological response to endogenous IL-7 stimulatory signals. Our data suggest that these defects are reversed during the immune reconstitution that follows HAART.