共抑制分子CD160在慢性HIV-1感染患者中的表达及临床意义

CD160 characterization and its association with disease progression in patients with chronic HIV-1 infection

目的 探讨慢性HIV-1感染者中CD4^＋和CD8^＋T细胞上共刺激分子CD160分子的表达及临床意义.方法 采集2010年1月至2011年12月解放军第三○二医院慢性HIV-1感染者23例（感染组）和20名健康人（对照组）的外周血,分离外周血单个核细胞,用直接免疫荧光染色方法标记并用流式细胞仪检测T细胞及Tn、Tcm、Tem和TemRA亚群上CD160表达的百分比及平均荧光强度（MFI）,并将CD160的表达水平与患者CD4^＋T细胞计数和病毒载量做相关性分析.结果 感染组中CD4^＋和CD8^＋T细胞上CD160表达均显著高于对照组[表达率：（14.3±7.5）％比（3.9±2.2）％和（40.9±13.2）％比（12.9±6.6）％;MFI：26.4±11.0比12.4±2.9和52.5 ±17.4比18.2±5.0];且CD4^＋T细胞上CD160的表达与CD4^＋T细胞计数呈负相关（r=-0.550,P=0.010）,和病毒载量呈正相关（r =0.522,P=0.015）,但CD8^＋T细胞上CD160的表达与CD4^＋T细胞计数和病毒载量无相关性.感染组CD8^＋T细胞Tn、Tcm、Tem亚群上CD160表达均显著高于对照组（25.3±17.6比5.0±3.1,45.8±13.0比20.4 ±4.3,37.0±13.6比20.0±10.8）,Tcm和Tem亚群上表达更高,且CD160＋ CD8^＋T细胞亚群中Tn比例降低而Tcm比例升高.结论 在慢性HIV-1感染中共抑制分子CD160的升高,可能与CD4^＋和CD8^＋T细胞的功能耗竭有关,且CD160可能主要对记忆性CD8^＋T细胞产生影响.

Objective To explore the expression of CD160,a costimulator,on CD4^＋ and CD8^＋ T cells in chronic human immunodeficiency virus-1 （HIV-1） infected patients.Methods A total of 23 chronic HIV-1 infected patients were enrolled into 302 Hospital of People＆#39;s Liberation Army from January 2010 to December 2011.Meanwhile,20 healthy individuals were selected as healthy controls （HC）.Peripheral blood was collected,peripheral blood mononuclear cells （PBMC） were isolated by density gradient centrifugation and CD160 was stained with fluorescent antibody.The expressions of CD160 on CD4^＋ and CD8^＋ T cell subsets were detected by flow cytometry and its correlation with CD4^＋ T cell absolute number and HIV RNA viral load were analyzed.Results The expressions of CD160 on CD4^＋ and CD8^＋ T cell increased versus HC （on CD4^＋ T cells,percentage：（14.3 ± 7.5） % vs （3.9 ± 2.2） %,median fluorescent intensity （MFI）：26.4 ± 11.0 vs 12.4 ± 2.9 ; on CD8^＋ T cells,percentage：（40.9 ± 13.2） % vs （12.9 ± 6.6） %,MFI：52.5 ± 17.4 vs 18.2 ± 5.0）.Furthermore,the expression of CD160 on CD4^＋ T cells was negatively correlated with CD4^＋ T cell absolute number （r =-0.550,P =0.010） and positively with HIV RNA load （r =0.522,P =0.015）.However,the expression of CD160 on CD8＋ T cells was not correlated with CD4^＋ T cell absolute number or HIV RNA load.The expressions of CD160 on CD8^＋ T cell subsets Tn,Tcm and Tem in patients with chronic HIV-1 infection increased compared with HC （25.3 ± 17.6vs5.0±3.1,45.8 ±13.0 vs20.4±4.3,37.0±13.6 vs20.0 ±10.8）.In addition,Tn subset decreased while Tcm subset increased in CD160 ＋ CD8^＋ T cell subset distribution in patients with HIV-1 infection compared with HC subjects.Conclusion CD160 may contribute to the exhaustion of CD4^＋ and CD8^＋ T cells and influence the distribution of memory CD8^＋ T cell subsets.