Perfetto S P, Hickey T E, Blair P J, Maino V C, Wagner K F, Zhou S, Mayers D L, St Louis D, June C H, Siegel J N
Henry M Jackson Foundation for the Advancement of Military Medicine, Rockville, Maryland 20852, USA.
Cytometry. 1997 Feb 15;30(1):1-9. doi: 10.1002/(sici)1097-0320(19970215)30:1<1::aid-cyto1>3.0.co;2-r.
Peripheral blood mononuclear cells from many asymptomatic HIV-infected patients exhibit defects in cytokine production and impaired proliferative responses in vitro but the mechanisms underlying this subclinical immune deficiency are controversial. To determine whether abnormalities in the earliest events following receptor engagement may help to explain the in vitro immune dysfunction, we measured the inducibility of the early activation marker CD69 in T cells from asymptomatic HIV-infected individuals in response to stimulation with anti-CD2 or anti-CD3 mAb. In a whole blood assay, we found that induction of CD69 was markedly impaired in CD4+ T cells from later-stage HIV-infected patients (CD4 counts 200-400/mm3) compared to uninfected controls. Among early stage patients (CD4 > 400/mm3), a subset (29%) had impaired CD69 induction. CD69 responses were equally depressed after stimulation through the CD3 or CD2 receptor pathways. Survey of a panel of immunophenotypic markers and propensity for apoptosis demonstrated a significant association between depressed induction of CD69 and decreased percentages of CD4+CD26+ and CD4+CD95+ cells but no association with the level of apoptosis. These data indicate that defects in T lymphocyte activation through CD3 and CD2 can be measured within hours of receptor stimulation in asymptomatic HIV-infected individuals and might be useful to monitor as an indicator of immune function in these patients.
许多无症状HIV感染患者的外周血单个核细胞在体外表现出细胞因子产生缺陷和增殖反应受损，但这种亚临床免疫缺陷的潜在机制存在争议。为了确定受体结合后最早事件中的异常是否有助于解释体外免疫功能障碍，我们测量了无症状HIV感染个体的T细胞中早期激活标志物CD69在抗CD2或抗CD3单克隆抗体刺激下的诱导能力。在全血试验中，我们发现与未感染的对照组相比，晚期HIV感染患者（CD4计数为200 - 400/mm³）的CD4⁺T细胞中CD69的诱导明显受损。在早期患者（CD4 > 400/mm³）中，一部分（29%）患者的CD69诱导受损。通过CD3或CD2受体途径刺激后，CD69反应同样受到抑制。对一组免疫表型标志物和凋亡倾向的调查显示，CD69诱导降低与CD4⁺CD26⁺和CD4⁺CD95⁺细胞百分比降低之间存在显著关联，但与凋亡水平无关。这些数据表明，在无症状HIV感染个体中，受体刺激后数小时内即可检测到通过CD3和CD2的T淋巴细胞激活缺陷，这可能有助于作为这些患者免疫功能的监测指标。
