Department of Clinical Immunology, Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark.
J Acquir Immune Defic Syndr. 2010 Mar;53(3):303-10. doi: 10.1097/QAI.0b013e3181ca3f7c.
CD4 T-cell recovery is impeded in some HIVinfected patients despite successful combination antiretroviral therapy (cART) with suppressed HIV RNA. We hypothesized that T-cell dysfunction would be increased in these patients.
In the Danish HIV Cohort Study, we identified HIV-1-infected patients initiating cART with a CD4 cell count <100 cells per microliter, followed by HIV RNA <50 copies per milliliter for 3 years. Patients with a CD4 count <200 cells per microliter after 3 years were identified as cases; 42 patients with a CD4 count > or = 200 cells per microliter were selected as controls. Six-color flow cytometry was performed on whole blood. Cytokine levels in supernatants from whole blood stimulations were assessed.
The case and control groups comprised 18 and 35 patients, respectively. Cases were older than controls (median: 54/46 years). The fraction of CD28+ cells was decreased among cases in the CD4+ and CD8+ T-cell subsets (P = 0.0014/P = 0.0349) and in the corresponding naive subsets (P = 0.0011/P , 0.0001). Cases had higher expression of human leukocyte antigen (HLA)-DR on naive CD4 and CD8 T cells (P = 0.0007/P = 0.0028). The production of interleukin (IL)-10 and IL-2 to phytohemagglutinin was decreased in cases (P < 0.0001/P = 0.019).
Patients with impaired CD4 recovery shared a dysregulated T-cell phenotype with low CD28, high HLA-DR expression, and low IL-2 and IL-10 production.
尽管接受了成功的联合抗逆转录病毒治疗（cART）并抑制了 HIV RNA，但一些 HIV 感染者的 CD4 细胞恢复仍受到阻碍。我们假设这些患者的 T 细胞功能障碍会增加。
在丹麦 HIV 队列研究中，我们确定了 CD4 细胞计数 <100 个/微升开始接受 cART 并 HIV RNA <50 拷贝/毫升持续 3 年的 HIV-1 感染者。在 3 年后 CD4 细胞计数 <200 个/微升的患者被确定为病例；选择 42 名 CD4 细胞计数 >或 = 200 个/微升的患者作为对照。对全血进行六色流式细胞术检测。评估全血刺激上清液中的细胞因子水平。
病例组和对照组分别包括 18 名和 35 名患者。病例组的年龄大于对照组（中位数：54/46 岁）。CD28+细胞在 CD4+和 CD8+T 细胞亚群（P = 0.0014/P = 0.0349）以及相应的幼稚亚群（P = 0.0011/P ，0.0001）中CD28+细胞的比例降低。病例组中幼稚 CD4 和 CD8 T 细胞上 HLA-DR 的表达更高（P = 0.0007/P = 0.0028）。病例组对植物血凝素产生的白细胞介素（IL）-10 和 IL-2 减少（P < 0.0001/P = 0.019）。
CD4 恢复受损的患者具有失调的 T 细胞表型，表现为 CD28 低、HLA-DR 表达高、IL-2 和 IL-10 产生低。
