Department of Pediatrics, CHU Saint-Pierre, Hôpital Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Clin Exp Immunol. 2011 Jul;165(1):77-84. doi: 10.1111/j.1365-2249.2011.04403.x. Epub 2011 Apr 19.
The objective of this study was to investigate whether the restored immune functions of vertically human immunodeficiency virus (HIV)-infected children who were severely immunodeficient before the initiation of highly active anti-retroviral therapy (HAART) are comparable to those of untreated slow progressors. We therefore assessed T cell proliferation and cytokine [interferon (IFN)-γ, interleukin (IL)-5 and IL-13] secretions after mitogen, recall antigens and HIV-1-specific stimulation in 12 untreated slow progressors, 16 untreated progressors and 18 treated patients. Treated children were profoundly immunodeficient before the initiation of HAART and had long-lasting suppression of viral replication on treatment. We demonstrated that slow progressors are characterized not only by the preservation of HIV-1-specific lymphoproliferative responses but also by the fact that these responses are clearly T helper type 1 (Th1)-polarized. Children on HAART had proliferative responses to HIV-1 p24 antigen, purified protein derivative (PPD) and tetanus antigen similar to slow progressors and higher than those of progressors. However, in contrast to slow progressors, most treated children exhibited a release of Th2 cytokines accompanying the IFN-γ secretion in response to the HIV-1 p24 antigen. Moreover, despite higher proliferative responses to phytohaemagglutinin (PHA) than the two groups of untreated children, treated children had lower levels of IFN-γ secretion in response to PHA than slow progressors. These data show that in severely immunodeficient vertically HIV-infected children, a long-lasting HAART allows recovering lymphoproliferative responses similar to untreated slow progressors. However, alterations in IFN-γ secretion in response to the mitogen PHA persisted, and their cytokine release after HIV-specific stimulation was biased towards a Th2 response.
本研究旨在探讨在开始高效抗逆转录病毒治疗（HAART）之前严重免疫缺陷的垂直感染人类免疫缺陷病毒（HIV）的儿童的免疫功能恢复情况是否与未经治疗的缓慢进展者相似。因此，我们评估了 12 名未经治疗的缓慢进展者、16 名未经治疗的进展者和 18 名接受治疗的患者在有丝分裂原、回忆抗原和 HIV-1 特异性刺激后 T 细胞增殖和细胞因子[干扰素（IFN）-γ、白细胞介素（IL）-5 和 IL-13]分泌情况。接受治疗的儿童在开始 HAART 之前存在严重的免疫缺陷，并且在治疗过程中病毒复制得到长期抑制。我们证明，缓慢进展者不仅具有保留的 HIV-1 特异性淋巴增殖反应的特征，而且这些反应明显呈辅助性 T 细胞 1（Th1）极化。接受 HAART 的儿童对 HIV-1 p24 抗原、纯化蛋白衍生物（PPD）和破伤风抗原的增殖反应与缓慢进展者相似，高于进展者。然而，与缓慢进展者不同的是，大多数接受治疗的儿童在对 HIV-1 p24 抗原的反应中伴随着 Th2 细胞因子的释放，表现出 IFN-γ的分泌。此外，尽管与未经治疗的两组儿童相比，接受治疗的儿童对植物血凝素（PHA）的增殖反应更高，但与缓慢进展者相比，接受治疗的儿童对 PHA 的 IFN-γ分泌水平较低。这些数据表明，在严重免疫缺陷的垂直感染 HIV 的儿童中，长期的 HAART 可恢复类似于未经治疗的缓慢进展者的淋巴增殖反应。然而，对有丝分裂原 PHA 的 IFN-γ分泌的改变仍然存在，并且它们在 HIV 特异性刺激后的细胞因子释放偏向 Th2 反应。
