Unaltered T cell responses to common antigens in individuals with Parkinson's disease.

Unaltered T cell responses to common antigens in individuals with Parkinson's disease.
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DOI:
10.1016/j.jns.2022.120510
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发表时间:
2023-01-15
影响因子:
4.4
通讯作者:
Sette, Alessandro
Sette, Alessandro
中科院分区:
医学3区
文献类型:
--
作者:
Williams, Gregory P.;Muskat, Kaylin;Frazier, April;Xu, Yaqian;Mateus, Jose;Grifoni, Alba;Antunes, Ricardo da Silva;Weiskopf, Daniela;Amara, Amy W.;Standaert, David G.;Goldman, Jennifer G.;Litvan, Irene;Alcalay, Roy N.;Sulzer, David;Arlehamn, Cecilia S. Lindestam;Sette, Alessandro

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帕金森病(PD)与炎症状态升高有关,包括激活的T细胞。然而,目前尚不清楚这些PD - T细胞反应是抗原特异性的还是更能表明全身性高反应性。我们的目的是测量和比较PD患者和年龄匹配的健康对照(HC)中针对来自常见人类病原体/疫苗的抗原的抗原特异性T细胞反应。筛选20例PD患者外周血单个核细胞(PBMCs)和19例年龄匹配的hc。抗原特异性T细胞反应通过流式细胞术检测,结合激活诱导标志物(AIM)测定和细胞内细胞因子染色。在这里,我们发现PD患者和hc患者对来自普通人群中常见的人类病原体/疫苗的几种抗原表现出相似的T细胞激活水平。同样,我们也观察到HC和PD在CD4和CD8 T细胞衍生细胞因子水平上对任何常见抗原的反应没有差异。这些抗原包括病毒(冠状病毒、鼻病毒、呼吸道合胞病毒、流感、巨细胞病毒)和细菌(百日咳、破伤风)靶标。这些结果表明,PD中观察到的T细胞功能障碍可能不会扩展到对常见抗原或疫苗靶抗原的异常反应。我们的研究支持这样一种观点,即PD中炎症T细胞反应的靶标可能更直接地针对α-突触核蛋白(α-syn)等自身抗原,而不是常见的外源抗原。
Parkinson’s disease (PD) is associated with a heightened inflammatory state, including activated T cells. However, it is unclear whether these PD T cell responses are antigen specific or more indicative of generalized hyperresponsiveness. Our objective was to measure and compare antigen-specific T cell responses directed towards antigens derived from commonly encountered human pathogens/vaccines in patients with PD and age-matched healthy controls (HC). Peripheral blood mononuclear cells (PBMCs) from 20 PD patients and 19 age-matched HCs were screened. Antigen specific T cell responses were measured by flow cytometry using a combination of the activation induced marker (AIM) assay and intracellular cytokine staining. Here we show that both PD patients and HCs show similar T cell activation levels to several antigens derived from commonly encountered human pathogens/vaccines in the general population. Similarly, we also observed no difference between HC and PD in the levels of CD4 and CD8 T cell derived cytokines produced in response to any of the common antigens tested. These antigens encompassed both viral (coronavirus, rhinovirus, respiratory syncytial virus, influenza, cytomegalovirus) and bacterial (pertussis, tetanus) targets. These results suggest the T cell dysfunction observed in PD may not extend itself to abnormal responses to commonly encountered or vaccine-target antigens. Our study supports the notion that the targets of inflammatory T cell responses in PD may be more directed towards autoantigens like α-synuclein (α-syn) rather than common foreign antigens.
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