T cell exhaustion is associated with cognitive status and amyloid accumulation in Alzheimer's disease.
T cell exhaustion is associated with cognitive status and amyloid accumulation in Alzheimer's disease.
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DOI：
10.1038/s41598-023-42708-8
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发表时间：
2023-09-22
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
过去100年的研究表明，炎症，传染病和阿尔茨海默病（AD）之间存在联系。了解免疫系统在AD发展过程中的变化可能有助于新的治疗方法。在这里，我们研究了一个老年队列谁已被评估为AD病理与淀粉样蛋白正电子发射断层扫描和认知测试，并进行了高维流式细胞术外周血单核细胞和脑脊液细胞。参与者被分为淀粉样蛋白阴性认知正常、淀粉样蛋白阳性认知正常（APCN）或淀粉样蛋白阳性轻度认知障碍（APMCI）（AD的早期阶段）。我们观察到外周先天免疫系统的主要改变，包括APMCI参与者血液中髓样和浆细胞样树突状细胞的增加。当检查适应性免疫系统时，淀粉样蛋白阳性的参与者，无论认知状态如何，CD 3 + T细胞增加。对CD 4+和CD 8 + T细胞的进一步分析显示，与认知正常的人相比，APMCI参与者具有更多分化表型T细胞的增加，例如效应记忆和效应记忆CD 45 RA表达（TEMRA）。当测量T细胞功能时，我们观察到与其他参与者相比，来自APCN参与者的T细胞具有增加的IFNγ+GzB产生细胞。相比之下，我们证明APMCI参与者在再刺激后缺乏细胞因子产生的T细胞大幅增加，并表达PD-1和Tox水平增加，表明这些细胞已经耗尽。这些细胞的复壮可能为AD提供潜在的治疗。
Studies over the last 100 years have suggested a link between inflammation, infectious disease, and Alzheimer’s Disease (AD). Understanding how the immune system changes during the development of AD may facilitate new treatments. Here, we studied an aging cohort who had been assessed for AD pathology with amyloid positron emission tomography and cognitive testing, and conducted high dimensional flow cytometry on peripheral blood mononuclear and cerebrospinal fluid cells. Participants were assigned a classification of being amyloid negative cognitively normal, amyloid positive cognitively normal (APCN), or amyloid positive mild cognitive impairment (APMCI), an early stage of AD. We observed major alterations in the peripheral innate immune system including increased myeloid and plasmacytoid dendritic cells in the blood of APMCI participants. When the adaptive immune system was examined, amyloid positive participants, regardless of cognitive status, had increased CD3+ T cells. Further analyses of CD4+ and CD8+ T cells revealed that APMCI participants had an increase in more differentiated phenotype T cells, such as effector memory and effector memory CD45RA expressing (TEMRA), compared to those with normal cognition. When T cell function was measured, we observed that T cells from APCN participants had increased IFNγ+GzB- producing cells compared to the other participants. In contrast, we demonstrate that APMCI participants had a major increase in T cells that lacked cytokine production following restimulation and expressed increased levels of PD-1 and Tox, suggesting these are exhausted cells. Rejuvenation of these cells may provide a potential treatment for AD.
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DOI：
10.1212/nxi.0000000000001106
发表时间：
2022-01
期刊：
Neurology(R) neuroimmunology & neuroinflammation
影响因子：
--
作者：
Joshi C;Sivaprakasam K;Christley S;Ireland S;Rivas J;Zhang W;Sader D;Logan R;Lambracht-Washington D;Rosenberg R;Cullum M;Hitt B;Li QZ;Barber R;Greenberg B;Cowell L;Zhang R;Stowe A;Huebinger R;Kelley B;Monson N
通讯作者：
Monson N
影响因子：
82.9
作者：
Baruch, Kuti;Deczkowska, Aleksandra;Schwartz, Michal
通讯作者：
Schwartz, Michal
DOI：
10.1016/j.jalz.2010.12.014
发表时间：
2011-07
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Breitner JC;Baker LD;Montine TJ;Meinert CL;Lyketsos CG;Ashe KH;Brandt J;Craft S;Evans DE;Green RC;Ismail MS;Martin BK;Mullan MJ;Sabbagh M;Tariot PN;ADAPT Research Group
通讯作者：
ADAPT Research Group
影响因子：
16.2
作者：
Allnutt, Mary Alice;Johnson, Kory;Jacobson, Steven
通讯作者：
Jacobson, Steven
影响因子：
9.9
作者：
BREITNER, JCS;GAU, BA;ANTHONY, JC
通讯作者：
ANTHONY, JC