HIV感染早期CD4^(+)T淋巴细胞各亚群及CCR5的表达特点

The expression characteristics of CD4^(+)T cell subgroups and CCR5 in the early stage of HIV infection

目的了解艾滋病病毒(HIV)感染早期CD4^(+)T淋巴细胞(简称CD4细胞)各亚群计数及其C-C趋化因子受体5(CCR5)的表达特点及其与疾病进展之间的相关性。方法选择HIV阴性对照者15例(对照组)和HIV急性期感染者40例,均来自北京佑安医院的男男性行为者(MSM)及HIV感染急性期队列,取HIV急性感染者第一次转阳时及转阳后30、90、180、360 d静脉血,常规进行CD4细胞计数测定;采用流式细胞分析术测定CD4细胞各亚群所占比例及其表面CCR5的表达情况。结果入组急性HIV感染者40例,根据疾病进展分成两组,CD4细胞高组为1年内CD4细胞数始终>450/μL 23例,CD4细胞低组为1年内进展到CD4细胞低于250/μL 17例。与对照组相比,感染后CD4细胞及CD4中心记忆细胞(CD4^(+)T_(CM))、CD4效应记忆细胞(CD4^(+)T_(EM))亚群在感染1年内绝对计数均有明显下降,CD4细胞及CD4^(+)T_(CM)亚群上CCR5的表达明显增加,但在不同感染时间点其变化差异均无统计学意义(P>0.05)。CD4细胞低组的CD4^(+)T_(CM)细胞表面CCR5表达水平较高(P<0.01),在HIV感染的第1年内两组的CD4^(+)T_(EM)细胞表面CCR5表达水平都高于CD4^(+)T_(CM)细胞亚群,而初始CD4细胞(CD4^(+)T_(naive))CCR5的表达水平最低。生存分析表明,CD4^(+)T_(CM)细胞和CD4^(+)T_(naive)细胞表面基线水平的CCR5表达与CD4细胞计数下降到250个/μL以下的时间相关(P<0.001),而CD4^(+)T_(EM)细胞表面CCR5表达水平却与之不相关(P=0.256)。结论HIV感染CD4^(+)T_(CM)细胞表面CCR5高表达与快速疾病进展密切相关。

Objective To identify dynamic characteristics of CD4^(+)T cell subsets and expression of C-C chemokine receptor 5(CCR5)and their relationships with disease progression during early stage of human immunodeficiency virus(HIV)infection.Methods HIV negative controls(n=15)and HIV acute infected individuals(n=40)were enrolled from the men who have sex with men(MSM)and HIV acute cohorts of Beijing You’an hospital.Blood samples were obtained from HIV acute infected individuals followed up at 30,90,180,360 days.Samples were collected and CD4^(+)T cell counts were examined routinely.The dynamic characteristics CD4^(+)T cell subsets and expression of CCR5 were measured by flow cytometry.Results Forty acute HIV-1 patients were enrolled.All individuals were divided into two groups according to the disease progression.One group included 23 patients whose CD4 cell counts was more than 450 cells/μL within two years(CD4 high group);the other group consisted of 17 patients whose CD4 cell counts was less than 250 cells/μL within two years(CD4 low group).Compared with the negative control,the absolute count of CD4 cells,central memory T cell(CD4^(+)T_(CM))and effector memory T cell(CD4^(+)T_(EM))subsets decreased significantly in one year after infection,and the expression of CCR5 on CD4^(+)T cells,CD4^(+)T_(naive)and CD4^(+)T_(CM)subsets increased significantly,but there was no significant difference at different infection time points.CCR5 expression was high on CD4^(+)T_(CM)cells in the CD4 low group(P<0.01).The expression of CCR5 in CD4^(+)T_(EM)cells in both groups was higher compared with CD4^(+)T_(CM)cells,with the lowest level of CCR5 expression being present on CD4^(+)T_(naive)cells during HIV-1 early infection.Log-rank(Mantel-Cox)test indicated that high levels of CCR5 on CD4^(+)T_(CM)and CD4^(+)T_(naive)subsets(P<0.001),but not on CD4^(+)T_(EM)cells(P=0.256),were associated with the time taken for CD4 counts to fall below 250 cells/mL.Conslusion A high CCR5 density on CD4^(+)T_(CM)cells in acute HIV infection might be associated with rapid disease progression.