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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Altered expression of the costimulatory molecules CD80, CD86, CD152, PD-1 and ICOS on T-cells from paracoccidioidomycosis patients: lack of correlation with T-cell hyporesponsiveness.
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Altered expression of the costimulatory molecules CD80, CD86, CD152, PD-1 and ICOS on T-cells from paracoccidioidomycosis patients: lack of correlation with T-cell hyporesponsiveness.

机译：共刺激分子CD80，CD86，CD152，PD-1和ICOS在副球菌病患者的T细胞上表达的改变：与T细胞反应不足无关。

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摘要

T-cell proliferative hyporesponsiveness, a hallmark of paracoccidioidomycosis immune responses, underlies host's failure in controlling fungus spread, being reversible with antifungal treatment. The mechanisms leading to this hypoproliferation are not well known. Since costimulatory molecules have been shown to profoundly regulate T-cell immune responses, we investigated the hypothesis that the determinants of the responder versus tolerant state may be the regulated expression of, or signaling by, costimulatory molecules. Expression of CD80, CD86, CD28, CD152, ICOS and PD-1 costimulatory molecules were examined on T-cells and monocytes harvested from stimulated and unstimulated PBMC cultures of active paracoccidioidomycosis patients and healthy individuals cured of past paracoccidioidomycosis. Stimuli were gp43, the immunodominant component of Paracoccidioides brasiliensis, and a Candida antigen. While CD28 expression, critical for optimal T-cell activation, was comparable between patients and controls, CD152, PD-1 and ICOS, which preferentially deliver negative signaling, were overexpressed on patients' stimulated and unstimulated T-cells. PBMC cultures were carried out in presence of the respective blocking antibodies which, however, failed to restore T-cell proliferation. CD80 and CD86 were equally expressed on patients' and controls' monocytes, but overexpressed on patients' T-cells. Blockade with the respective blocking antibodies on day 4 of the culture also did not restore T-cell proliferation, while, on day 0, differentially inhibited Candida and gp43 responses, suggesting that different antigens require different costimulatory pathways for antigen presentation. Our data favors the hypothesis, raised from other foreign antigen models, that prolonged in vivo antigen exposure leads to an adaptive tolerance T-cell state which is hardly reverted in vitro.
机译：T细胞增殖性低反应性是副球孢子菌病免疫反应的标志，是宿主无法控制真菌扩散的基础，可通过抗真菌治疗来逆转。导致这种过度增殖的机制尚不清楚。由于共刺激分子已显示出深刻调节T细胞免疫反应的能力，因此我们研究了以下假设：响应者对耐受状态的决定因素可能是共刺激分子的调控表达或信号传导。在从活跃和未受刺激的PBC培养的球状副球菌病患者和治愈过往副球菌病的健康个体的T细胞和单核细胞上检查了CD80，CD86，CD28，CD152，ICOS和PD-1共刺激分子的表达。刺激物是gp43，巴西副球菌的免疫主要成分和念珠菌抗原。尽管CD28表达对于最佳T细胞活化至关重要，但在患者和对照组之间相当，而CD152，PD-1和ICOS（优先传递阴性信号）在患者刺激和未刺激的T细胞上过度表达。在各自的阻断抗体的存在下进行PBMC培养，但是其不能恢复T细胞增殖。 CD80和CD86在患者和对照组的单核细胞上均等表达，但在患者的T细胞上过表达。在培养的第4天用相应的阻断抗体进行阻断也不能恢复T细胞增殖，而在第0天，差异抑制了念珠菌和gp43反应，表明不同的抗原需要不同的共刺激途径来呈递抗原。我们的数据支持从其他外来抗原模型提出的假说，即体内抗原暴露时间延长会导致适应性耐受性T细胞状态，这种状态在体外几乎无法恢复。

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