Boulassel Mohamed-Rachid, Mercier Francois, Gilmore Norbert, Routy Jean-Pierre
Immunodeficiency Service, Montreal Chest Institute, McGill University Health Centre, Montreal, Quebec, Canada.
Clin Immunol. 2007 Aug;124(2):149-57. doi: 10.1016/j.clim.2007.05.005. Epub 2007 Jun 11.
Evidence from animal models suggests that the expression of CD8alphaalpha homodimer on CD8(+) T cells plays a key role in the generation of long-lived memory cells. Here, we studied the quantitative alterations of CD8(+) T cell subsets expressing CD8alphaalpha, interleukin-7 receptor (IL-7Ralpha) and activation markers in HIV-1-infected individuals including aviremic, viremic and slow progressor subjects using eight-color flow cytometry. Compared to slow progressor subjects, expression of CD8alphaalpha was significantly reduced in aviremic and viremic patients and this reduction occurred mainly within central memory cell subsets and not in naive and effector memory compartments. Persistence of antigenemia leads to IL-7Ralpha loss mainly on central and pre-terminal memory CD8(+) T cell subsets in viremic patients but not in slow progressor subjects. Compared to aviremic and viremic patients, slow progressor subjects had lower levels of IL-7 and reduced activated cells. The expression of CD8alphaalpha was not significantly related to IL-7Ralpha although negative associations were evidenced within all CD8(+) T cell subsets. Collectively, these results further advance the characterization of immunophenotypic patterns of CD8(+) T cell subsets expressing CD8alphaalpha/IL-7Ralpha and provide new insights into the ability of HIV-1 infection to alter memory cell population.
来自动物模型的证据表明,CD8(+) T细胞上CD8αα同型二聚体的表达在长寿记忆细胞的产生中起关键作用。在此,我们使用八色流式细胞术研究了HIV-1感染个体(包括病毒血症阴性、病毒血症阳性和疾病缓慢进展者)中表达CD8αα、白细胞介素-7受体(IL-7Rα)和激活标志物的CD8(+) T细胞亚群的定量变化。与疾病缓慢进展者相比,病毒血症阴性和病毒血症阳性患者中CD8αα的表达显著降低,这种降低主要发生在中枢记忆细胞亚群内,而不是在初始和效应记忆区室中。病毒血症的持续存在导致IL-7Rα主要在病毒血症阳性患者的中枢和终末前记忆CD8(+) T细胞亚群上丢失,但在疾病缓慢进展者中没有。与病毒血症阴性和病毒血症阳性患者相比,疾病缓慢进展者的IL-7水平较低且活化细胞减少。CD8αα的表达与IL-7Rα没有显著相关性,尽管在所有CD8(+) T细胞亚群中都有负相关的证据。总体而言,这些结果进一步推进了对表达CD8αα/IL-7Rα的CD8(+) T细胞亚群免疫表型模式的表征,并为HIV-1感染改变记忆细胞群体的能力提供了新的见解。