HIV-1慢性感染者CD39^+PD-1^+CD4^+T淋巴细胞特点与抗病毒治疗疗效的关系

Characteristics of CD39+PD-1+CD4 lymphocyte cells and their associations with the efficacy of antiretroviral therapy in chronic HIV-1-infected patients

目的通过分析1型艾滋病病毒(HIV-1)感染者不同疾病阶段CD39^+PD-1^+CD4^+T淋巴细胞(简称CD39^+PD-1^+CD4细胞)的特点及其与潜伏病毒库形成的关系,探讨CD39^+PD-1^+CD4细胞的临床意义。方法通过流式细胞术检测CD4细胞上CD39及PD-1的表达情况,分析CD39^+PD-1^+CD4细胞与CD4细胞计数、病毒载量及CD4细胞内病毒指标的相关性。通过实时荧光定量聚合酶链反应(PCR)检测免疫重建成功患者(CRs)和免疫重建失败患者(INRs)的HIV库,分析CD39^+PD-1^+CD4细胞与HIV库的关系。结果入组11例健康对照(HCs)和69例HIV-1感染者,其中包括38例未抗病毒治疗(ART)者(TNs)、21例CRs、10例INRs。(1)与HCs相比,TNs组患者CD39^+PD-1^+CD4细胞亚群占比显著升高(平均值0.99%vs.2.50%);与TNs组相比,ART后,CRs组患者的CD39^+PD-1^+CD4细胞亚群占比显著降低(平均值2.50%vs.0.86%);而INRs组患者该细胞亚群占比显著高于CRs组(平均值2.74%vs.0.86%);(2)在TNs组患者中CD39^+PD-1^+CD4细胞亚群占比与CD4细胞计数呈负相关(r=-0.3596,P=0.0266),与病毒载量呈正相关(r=0.4511,P=0.0045);(3)ART两年以上患者CD39^+PD-1^+CD4细胞亚群占比与HIV脱氧核糖核酸(HIV DNA)正相关(r=0.5659,P=0.0473),与细胞相关的未剪接HIV核糖核酸(HIV us RNA)正相关(r=0.6758,P=0.0137)。结论CD39^+PD-1^+CD4细胞与ART后免疫重建失败相关,其机制可能是CD39^+PD-1^+CD4细胞促进HIV建立潜伏病毒库。

Objective To clarify the characteristics of CD39^+PD-1^+CD4^+ T lymphocyte cells in different stages of HIV-1 infection and the relationship between CD39^+PD-1^+CD4 cells and HIV-1 reservoir after ART in HIV-1-infected individuals, and further evaluate the clinical significance of CD39^+PD-1^+CD4 cell during AIDS disease progression. Methods 69 patients including 38 treatment na?ve patients(TNs), 21 complete responders(CRs), and 10 immunological non-responders(INRs) were enrolled in this study. 11 HCs were enrolled as control. The expression of CD39 and PD-1 on CD4 cells was detected by flow cytometry. The frequency of CD39^+PD-1^+CD4 cells, and its correlations with viral load and CD4 cell count were analyzed in TNs. The associations between the frequency of CD39^+PD-1^+CD4 cells and HIV DNA or HIV usRNA, detected by qRT-PCR, were analyzed in CRs and INRs. Results 1) Compared with HCs, TNs showed significantly increased frequency of CD39^+PD-1^+CD4 cells(mean 0.99% vs 2.50%);CD39^+PD-1^+CD4 cells(mean 2.50% vs 0.86%) significantly increased in TNs compared with the CRs;INRs showed significantly higher frequency of CD39^+PD-1^+CD4 cells than CRs(mean 2.74% vs 0.86%);2) In TNs, the frequency of CD39^+PD-1^+CD4 cells was negatively correlated with that of CD4 cell count(r =-0.3596, P =0.0266), and positively correlated with viral load(r =0.4511, P =0.0045). 3) The frequency of CD39^+PD-1^+CD4 cell subsets in patients with antiretroviral therapy(ART) for more than two years was positively correlated with HIV DNA(r=0.5659, P=0.0473) and cell-associated HIV usRNA(r=0.6758, P =0.0137). Conclusion Expansion of CD39^+PD-1^+CD4 cells is associated with poor immune reconstitution after ART. The mechanism may be that CD39^+PD-1^+CD4 cells promote the establishment of HIV latent reservoir.