Immunological dysfunction in HIV-1-infected individuals caused by impairment of adenosine deaminase-induced costimulation of T-cell activation
Immunological dysfunction in HIV-1-infected individuals caused by impairment of adenosine deaminase-induced costimulation of T-cell activation
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DOI：
10.1111/j.1365-2567.2009.03121.x
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发表时间：
2009-11-01
期刊：
影响因子：
6.4
通讯作者：
Franco, Rafael
中科院分区：
文献类型：
--
作者：
Martinez-Navio, Jose M.;Climent, Nuria;Franco, Rafael
CD26和腺苷脱氨酶(ADA)之间的细胞表面结合在T细胞激活过程中具有协同刺激功能。一些研究揭示了CD4+CD26+T细胞耗竭、血清ADA水平升高和人类免疫缺陷病毒(HIV)感染的演变之间的相关性，暗示CD26和ADA参与了HIV疾病的进展。在此背景下，我们的目标是确定在HIV感染期间ADA共刺激信号是否可以改变。从细胞增殖和细胞因子分泌的角度，对36例HIV感染者的细胞进行AdA共刺激作用的研究。在HIV-1感染者中发现ADA对T细胞增殖的影响，并与CD_4~+百分率和最低CD_4计数呈正相关，与病毒载量呈负相关，表明ADA的反应依赖于患者的免疫状态。ADA诱导的细胞因子[干扰素(干扰素)-γ、白介素6和白介素10]在HIV-1感染者T细胞中的产生显著减少。为了消除与HIV-1感染患者免疫缺陷相关的一些变量，在重组糖蛋白120(Gp120)存在的情况下，对来自健康志愿者的T细胞进行了抗CD3+ADA检测。研究发现，gp120参与了ADA-CD26相互作用的损伤，从而导致了ADA对共刺激和细胞因子产生的影响。Gp120介导的CD26-ADA相互作用的破坏是一种新的机制，可能至少部分解释了HIV-1感染患者的免疫学特征的改变，并可能与艾滋病的发病机制有重要关系。
P>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.