Kampmann Beate, Tena-Coki Gwen N, Nicol Mark P, Levin Michael, Eley Brian
School of Child and Adolescent Health, University of Cape Town, and Red Cross Children's Hospital, Rondebosch, Cape Town 7701, Republic of South Africa.
AIDS. 2006 Apr 24;20(7):1011-8. doi: 10.1097/01.aids.0000222073.45372.ce.
Recent epidemiological studies in adults suggest that HAART can prevent the development of tuberculosis in HIV-infected individuals, but the mechanisms are incompletely understood and no data exist in children. We investigated whether changes in mycobacterial-specific immune responses can be demonstrated in children after commencing antiretroviral therapy.
We measured mycobacterial growth in vitro using a novel whole-blood assay employing reporter-gene tagged bacillus Calmette-Guérin (BCG) in a prospective cohort study in the tuberculosis-endemic environment of South Africa. Key cytokines were measured in supernatants collected from the whole-blood assay using cytometric bead array.
A cohort of 15 BCG-vaccinated HIV-infected children was evaluated prospectively for in-vitro antimycobacterial immune responses before and during the first year of HAART. All children had advanced HIV disease. Nine children completed all study timepoints.
Before HAART, blood from children showed limited ability to restrict the growth of mycobacteria in the functional whole-blood assay. The introduction of HAART was followed by rapid and sustained reconstitution of specific antimycobacterial immune responses, measured as the decreased growth of mycobacteria. IFN-gamma levels in culture supernatants did not reflect this response; however, a decline in TNF-alpha was observed.
This is the first study using a functional in-vitro assay to assess the effect of HAART on immune responses to mycobacteria in HIV-infected children. Our in-vitro data mirror the in-vivo observation of decreased susceptibility to tuberculosis in HIV-infected adults receiving antiretroviral agents. This model may be useful for further characterizing immune reconstitution after HAART.
近期针对成人的流行病学研究表明，高效抗逆转录病毒治疗（HAART）可预防HIV感染者患结核病，但其中的机制尚未完全明确，且尚无关于儿童的数据。我们调查了开始抗逆转录病毒治疗后，儿童体内分枝杆菌特异性免疫反应是否会发生变化。
在南非结核病流行地区进行的一项前瞻性队列研究中，我们使用一种新型全血检测方法，即利用报告基因标记的卡介苗（BCG）来测量体外分枝杆菌的生长情况。使用细胞计数珠阵列检测从全血检测中收集的上清液中的关键细胞因子。
对15名接种卡介苗的HIV感染儿童组成的队列进行前瞻性评估，在HAART治疗的第一年之前及期间检测其体外抗分枝杆菌免疫反应。所有儿童均患有晚期HIV疾病。9名儿童完成了所有研究时间点的检测。
在HAART治疗前，儿童的血液在功能性全血检测中显示出限制分枝杆菌生长的能力有限。引入HAART治疗后，则出现了特异性抗分枝杆菌免疫反应的快速且持续重建，表现为分枝杆菌生长减少。培养上清液中的γ干扰素水平并未反映出这种反应；然而，观察到肿瘤坏死因子-α水平有所下降。
这是第一项使用功能性体外检测方法来评估HAART对HIV感染儿童抗分枝杆菌免疫反应影响的研究。我们的体外数据反映了在接受抗逆转录病毒药物治疗的HIV感染成人中，对结核病易感性降低的体内观察结果。该模型可能有助于进一步明确HAART治疗后的免疫重建情况。
