Department of Biochemistry and Molecular Biology, Faculty of Biology, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
Immunology. 2009 Nov;128(3):393-404. doi: 10.1111/j.1365-2567.2009.03121.x.
The cell surface association between CD26 and adenosine deaminase (ADA) has a costimulatory function during T-cell activation. Several studies have revealed correlations among CD4(+) CD26(+) T-cell depletion, increased serum levels of ADA, and the evolution of human immunodeficiency virus (HIV) infection, implicating CD26 and ADA in HIV disease progression. In this context, we aimed to determine whether ADA costimulation could be altered during HIV infection. ADA costimulation was investigated in cells from HIV-infected patients (n = 36) in terms of proliferation and cytokine secretion. An effect of ADA on T-cell proliferation was found in HIV-1-infected patients and correlated positively with the CD4(+) percentage and the nadir CD4 count and negatively with viral load, demonstrating that the response depends on the immunological status of the patient. The robust ADA-induced increase in cytokine production [interferon (IFN)-gamma, interleukin (IL)-6 and IL-10] was markedly reduced in T cells from HIV-1-infected subjects. To eliminate some of the variables associated with immunological defects in HIV-1-infected patients, anti-CD3 plus ADA assays with T cells from healthy volunteers were performed in the presence of recombinant glycoprotein 120 (gp120). It was found that gp120 was responsible for the impairment of the ADA-CD26 interaction and consequently of the ADA-induced effect on both costimulation and cytokine production. The gp120-mediated disruption of the CD26-ADA interaction is a novel mechanism that might explain, at least in part, the altered immunological features observed in HIV-1-infected patients and may have significant relevance in AIDS pathogenesis.
CD26 与腺苷脱氨酶（ADA）在细胞表面的结合在 T 细胞激活过程中具有共刺激功能。几项研究表明，CD4+CD26+T 细胞耗竭、血清 ADA 水平升高以及人类免疫缺陷病毒（HIV）感染的演变之间存在相关性，这表明 CD26 和 ADA 参与了 HIV 疾病的进展。在这种情况下，我们旨在确定 HIV 感染过程中 ADA 的共刺激是否会发生变化。我们从 HIV 感染患者（n=36）的细胞中研究了 ADA 的共刺激作用，包括增殖和细胞因子分泌。发现 ADA 对 HIV-1 感染患者的 T 细胞增殖有影响，并且与 CD4+百分比、CD4 计数的最低点呈正相关，与病毒载量呈负相关，表明该反应取决于患者的免疫状态。ADA 诱导的细胞因子产生增加（干扰素（IFN）-γ、白细胞介素（IL）-6 和 IL-10）在 HIV-1 感染患者的 T 细胞中显著降低。为了消除与 HIV-1 感染患者免疫缺陷相关的一些变量，我们用重组糖蛋白 120（gp120）在健康志愿者的 T 细胞中进行了抗 CD3 加 ADA 检测。结果发现，gp120 是导致 ADA-CD26 相互作用受损以及随后 ADA 对共刺激和细胞因子产生的影响受损的原因。gp120 介导的 CD26-ADA 相互作用的破坏是一种新的机制，至少可以部分解释在 HIV-1 感染患者中观察到的改变的免疫特征，并且可能在 AIDS 发病机制中具有重要意义。
