Colle J-H, Moreau J-L, Fontanet A, Lambotte O, Joussemet M, Delfraissy J-F, Thèze J
Unité Immunogénétique Cellulaire, Département de Médecine Moléculaire, Institut Pasteur, 25-28 rue du Dr. Roux, 75724 Paris Cedex 15, France.
Clin Exp Immunol. 2006 Mar;143(3):398-403. doi: 10.1111/j.1365-2249.2006.03022.x.
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 interleukin (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.
HIV感染会异常激活免疫系统，慢性期伴有CD8细胞区的显著改变。本文分析并报道了HIV感染患者中记忆性CD8 T淋巴细胞CD127（IL-7Rα链）的表达情况。记忆性CD8 T细胞亚群通过CD45RA和CD27标志物的表达来表征，CD127细胞表面表达通过四色流式细胞术进行体外检测。HIV感染与记忆性CD8淋巴细胞中CD127(+)细胞比例下降有关，这导致HIV感染患者中CD127(-) CD45RA(-)CD27(+) CD8 T细胞计数更高。在该亚群中还观察到阳性细胞的CD127细胞表面表达[平均荧光强度（MFI）]降低。数据表明，高效抗逆转录病毒疗法（HAART）可逆转这些缺陷。还在体外研究了CD127表达的调节。在健康供体和HAART患者的记忆性CD8淋巴细胞中观察到白细胞介素（IL）-7对CD127的下调作用。在无IL-7培养条件下记忆性CD8淋巴细胞的CD127表达证实，病毒血症患者的IL-7R调节发生改变。在相同实验条件下，HAART患者的记忆性CD8淋巴细胞显示出与健康个体细胞相当的CD127表达水平。HIV感染患者记忆性CD8 T淋巴细胞中CD127细胞表面表达改变和CD127调节缺陷是这些细胞在内源性IL-7刺激信号生理反应中可能受到阻碍的潜在机制。我们的数据表明，这些缺陷在HAART后的免疫重建过程中会得到逆转。
