The role of apoptosis in the antigen-specific T cell hyporesponsiveness of paracoccidioidomycosis patients
The role of apoptosis in the antigen-specific T cell hyporesponsiveness of paracoccidioidomycosis patients
复制标题
DOI：
10.1006/clim.2002.5272
复制
发表时间：
2002-11-01
影响因子：
8.6
通讯作者：
Benard, G
中科院分区：
文献类型：
--
作者：
Cacere, CR;Romano, CC;Benard, G
副球囊霉菌病是一种与抗原特异性免疫缺陷相关的深度地方性真菌病。为探讨细胞凋亡在这一免疫缺陷中的作用，用巴西拟球孢子菌主抗原(Gp43)和非相关真菌抗原(来自白色念珠菌的CMA)刺激外周血单个核细胞(PBMC)，用流式细胞仪检测膜联蛋白V和碘化丙啶染色。对照PBMC在两种抗原作用下增殖良好。患者的PBMC仅在CMA的刺激下增殖，但在gp43和CMA的刺激下表现出比他们自己未刺激的培养中更高的凋亡水平。此外，对照组PBMC中gp43诱导的细胞凋亡率低于患者组。因此，患者但不是对照组，经gp43刺激的T细胞明显保持清醒状态，随后发生了凋亡。虽然CMA诱导的细胞凋亡可能是由激活诱导的细胞死亡触发的，但在gp43诱导的细胞凋亡中显然不是这样，因为gp43刺激的培养物中缺乏细胞周期和IL-2。然而，在gp43刺激的患者PBMC培养中发现更高的IL-10水平。在培养中加入中和抗IL-10抗体，仅在gp43刺激的患者PBMC培养中导致细胞凋亡水平增加。我们的结果表明，细胞凋亡在患者的抗原特异性低反应性中起作用，而IL-10可能具有抗细胞凋亡的作用。(C)2002年埃尔塞维尔科学公司(美国)。
Paracoccidioidomycosis is a deep endemic mycosis associated with an antigen-specific immunodeficiency. To examine the role of apoptosis in this immunodeficiency, peripheral blood mononuclear cells (PBMC) of patients with paracoccidioidomycosis and controls were stimulated with the main antigen of Paracoccidioides brasiliensis (gp43) and an unrelated fungal antigen (from Candida albicans, CMA) and analyzed for annexin V and propidium iodide staining by flow cytometry. Control PBMC proliferated well with both antigens. Patients' PBMC proliferated only with CMA, but presented higher levels of apoptosis with gp43 and CMA than in their own unstimulated cultures. Moreover, gp43-triggered apoptosis in control PBMC was lower than in those of the patients. Thus, patient but not control gp43-stimulated T cells apparently remained anergized and subsequently underwent apoptosis. While CMA-induced apoptosis is likely triggered by activation-induced cell death, this is apparently not the case in gp43-induced apoptosis because of the lack of cell cycling and IL-2 in the gp43-stimulated cultures. However, higher IL-10 levels were found in gp43-stimulated patient PBMC cultures. Addition of a neutralizing anti-IL-10 antibody to the cultures resulted in increased apoptosis levels only in gp43-stimulated patient PBMC cultures. Our results suggest that apoptosis plays a role in the patients' antigen-specific hyporesponsiveness and that IL-10 may have an antiapoptotic role. (C) 2002 Elsevier Science (USA).