Lange Christoph G, Xu Zhan, Patterson Bruce K, Medvik Kathy, Harnisch Brooke, Asaad Robert, Valdez Hernan, Lee Sandra J, Landay Alan, Lieberman Judy, Lederman Michael M
Center for AIDS Research, Department of Medicine, Division of Infectious Diseases, Case Western Reserve University, University Hospitals of Cleveland, 2061 Cornell Road, Cleveland, OH 44106, USA.
AIDS. 2004 Mar 5;18(4):605-13. doi: 10.1097/00002030-200403050-00004.
To ascertain whether lymphoproliferation (LP) responses to HIVp24 in chronically infected patients treated with antiretroviral therapy (ART) predict an improved cytolytic T-cell phenotype or better in vivo immune function as measured by immunization responses.
HIV-infected patients who started ART during chronic infection and who achieved viral suppression (HIV-RNA < 400 copies/ml for > 12 months) were grouped by the presence of strong [stimulation index (SI) > 10; n = 21] or absent (SI < 3; n = 18) LP to HIV-core antigen. The two groups were compared for functional immune responses to vaccination with diphtheria-toxoid, tetanus-toxoid and keyhole-limpet-hemocyanin, frequency of circulating naive and memory CD4+ and CD8+ T lymphocytes, maturation phenotype and expression of cytolytic molecules on total and HIV-specific CD8+ T cells, and frequency of memory CD4+ T cells with intracellular HIV-mRNA. Group comparisons were analyzed by non-parametric Mann-Whitney tests. Proportions were estimated by Pearson's chi analysis.
There were no differences between the groups in immune responses to vaccination or in the numbers or phenotype of circulating T cells. In a subgroup of HLA-A2+ or B8+ patients, HIV-reactive CD8+ T cells in both groups had similar expression of perforin, granzyme A and T-cell maturation markers (CD27, CD28, CCR7, CD62L). However, patients with SI > 10 in response to HIVp24 tended to more often have high levels of circulating CD4+ T cells with intracellular HIV-1 mRNA than did patients with SI < 3.
Following long-standing suppression of viral replication on ART, the presence of HIV-1 specific T-helper proliferation responses does not correlate with improved indices of immune phenotype or function but may reflect relatively higher levels of HIV-expression.
确定接受抗逆转录病毒疗法（ART）治疗的慢性感染患者对HIV p24的淋巴细胞增殖（LP）反应是否能预测细胞溶解性T细胞表型改善或通过免疫反应测量的更好的体内免疫功能。
在慢性感染期间开始接受ART并实现病毒抑制（HIV-RNA<400拷贝/ml超过12个月）的HIV感染患者，根据对HIV核心抗原的强LP反应（刺激指数（SI）>10；n = 21）或无LP反应（SI<3；n = 18）进行分组。比较两组对白喉类毒素、破伤风类毒素和钥孔血蓝蛋白疫苗接种的功能性免疫反应、循环中幼稚和记忆性CD4+和CD8+ T淋巴细胞的频率、成熟表型以及总CD8+ T细胞和HIV特异性CD8+ T细胞上细胞溶解分子的表达，以及具有细胞内HIV-mRNA的记忆性CD4+ T细胞的频率。组间比较采用非参数曼-惠特尼检验进行分析。比例通过Pearson卡方分析进行估计。
两组在疫苗接种的免疫反应或循环T细胞的数量或表型方面没有差异。在HLA-A2+或B8+患者亚组中，两组的HIV反应性CD8+ T细胞在穿孔素、颗粒酶A和T细胞成熟标志物（CD27、CD28、CCR7、CD62L）的表达上相似。然而，对HIV p24反应SI>10的患者比SI<3的患者更常出现具有细胞内HIV-1 mRNA的循环CD4+ T细胞高水平。
在ART治疗使病毒复制长期受到抑制后，HIV-1特异性T辅助细胞增殖反应的存在与免疫表型或功能指标的改善无关，但可能反映了相对较高水平的HIV表达。
