Parkinson's disease and immunological abnormalities: increase of HLA-DR expression on monocytes in cerebrospinal fluid and of CD45RO+ T cells in peripheral blood

Analysis of peripheral blood mononuclear cells demonstrated that α-synuclein–specific T cells are active in preclinical and early Parkinson’s disease.

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Reduced Immunosenescence of Peripheral Blood T Cells in Parkinson’s Disease with CMV Infection Background

International Journal of Molecular Sciences ◽

10.3390/ijms222313119 ◽

2021 ◽

Vol 22 (23) ◽

pp. 13119

Author(s):

Julia D. Vavilova ◽

Anna A. Boyko ◽

Natalya V. Ponomareva ◽

Vitaly F. Fokin ◽

Ekaterina Y. Fedotova ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

T Cells ◽

T Cell ◽

Nk Cells ◽

Chronic Inflammation ◽

Peripheral Blood ◽

Effector Memory ◽

Cmv Infection ◽

Healthy Donors

Immunosenescence is a process of remodeling the immune system under the influence of chronic inflammation during aging. Parkinson’s disease (PD) is a common age-associated neurodegenerative disorder and is frequently accompanied by neuroinflammation. On the other hand, cytomegalovirus (CMV), one of the most spread infections in humans, may induce chronic inflammation which contributes to immunosenescence, differentiation and the inflation of T cells and NK cells. Currently, there is no clear understanding of immunosenescence severity in PD patients infected with CMV. In this study, we analyzed differentiation stages and immunosenescence characteristics of T cells and NK cells in 31 patients with mild and moderate PD severity, 33 age-matched and 30 young healthy donors. The PD patients were 100% CMV-seropositive compared to 76% age-matched and 73% young CMV-infected healthy donors. The proportion of effector memory T cells re-expressing CD45RA, CD57+CD56− T cells and CD57+CD56+ T cells was significantly reduced in PD patients compared with CMV-seropositive age-matched healthy individuals. The CD57+CD56− T cell proportion in PD patients was similar to that of CMV-seropositive young healthy donors. Thus, PD is characterized by reduced peripheral blood T cell immunosenescence, even against the background of CMV infection.

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Single-cell transcriptome and TCR profiling reveal activated and expanded T cell populations in Parkinson’s disease

Cell Discovery ◽

10.1038/s41421-021-00280-3 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Pingping Wang ◽

Lifen Yao ◽

Meng Luo ◽

Wenyang Zhou ◽

Xiyun Jin ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

T Cells ◽

Cerebrospinal Fluid ◽

T Cell ◽

Single Cell ◽

Neuronal Degeneration ◽

Large Population ◽

Cell Transcriptome ◽

Single Cell Transcriptome

AbstractGiven the chronic inflammatory nature of Parkinson’s disease (PD), T cell immunity may be important for disease onset. Here, we performed single-cell transcriptome and TCR sequencing, and conducted integrative analyses to decode composition, function and lineage relationship of T cells in the blood and cerebrospinal fluid of PD. Combined expression and TCR-based lineage tracking, we discovered a large population of CD8+ T cells showing continuous progression from central memory to terminal effector T cells in PD patients. Additionally, we identified a group of cytotoxic CD4+ T cells (CD4 CTLs) remarkably expanded in PD patients, which derived from Th1 cells by TCR-based fate decision. Finally, we screened putative TCR–antigen pairs that existed in both blood and cerebrospinal fluid of PD patients to provide potential evidence for peripheral T cells to participate in neuronal degeneration. Our study provides valuable insights and rich resources for understanding the adaptive immune response in PD.

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Specific immune status in Parkinson’s disease at different ages of onset

npj Parkinson s Disease ◽

10.1038/s41531-021-00271-x ◽

2022 ◽

Vol 8 (1) ◽

Author(s):

Jun Tian ◽

Shao-Bing Dai ◽

Si-Si Jiang ◽

Wen-Yi Yang ◽

Yi-Qun Yan ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

T Cells ◽

Nk Cells ◽

Peripheral Blood ◽

Rating Scale ◽

Immune Status ◽

Immune Cell ◽

Late Onset ◽

Different Ages

AbstractRecent evidence suggests that innate and adaptive immunity play a crucial role in Parkinson’s disease (PD). However, studies regarding specific immune cell classification in the peripheral blood in PD remain lacking. Therefore, we aimed to explore the different immune status in patients with PD at different ages of onset. We included 22 patients; among them were 10 who had early-onset PD (EOPD) and 12 had late-onset PD (LOPD) and 10 young healthy controls (YHCs) and 8 elder HCs (EHCs). Mass cytometry staining technology was used to perform accurate immunotyping of cell populations in the peripheral blood. Motor symptoms and cognitive function were assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) III score and Mini-mental State Examination (MMSE) score, respectively. T test and ANOVA statistical analysis were performed on the frequency of annotated cell population. Linear regression model was used to analyze the correlation between clusters and clinical symptoms. We characterized 60 cell clusters and discovered that the immune signature of PD consists of cluster changes, including decreased effector CD8+ T cells, lower cytotoxicity natural killer (NK) cells and increased activated monocytes in PD patients. In summary, we found that CD8+ T cells, NK cells, and monocytes were associated with PD. Furthermore, there may be some differences in the immune status of patients with EOPD and LOPD, suggesting differences in the pathogenesis between these groups.

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CHAPTER 9: Immunology of TBEV-Infections

Tick-borne encephalitis - The Book ◽

10.33442/26613980_9-3 ◽

2020 ◽

Keyword(s):

Central Nervous System ◽

T Cells ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Nk Cells ◽

Peripheral Blood ◽

Sample Collection ◽

Tick Borne Encephalitis ◽

Viral Infectious Disease ◽

The Central Nervous System

Tick-borne encephalitis (TBE) is a viral infectious disease of the central nervous system caused by the tick-borne encephalitis virus (TBEV). TBE is usually a biphasic disease and in humans the virus can only be detected during the first (unspecific) phase of the disease. Pathogenesis of TBE is not well understood, but both direct viral effects and immune-mediated tissue damage of the central nervous system may contribute to the natural course of TBE. The effect of TBEV on the innate immune system has mainly been studied in vitro and in mouse models. Characterization of human immune responses to TBEV is primarily conducted in peripheral blood and cerebrospinal fluid, due to the inaccessibility of brain tissue for sample collection. Natural killer (NK) cells and T cells are activated during the second (meningo-encephalitic) phase of TBE. The potential involvement of other cell types has not been examined to date. Immune cells from peripheral blood, in particular neutrophils, T cells, B cells and NK cells, infiltrate into the cerebrospinal fluid of TBE patients.

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Faculty Opinions recommendation of Diagnostic biomarkers for Parkinson's disease: focus on α-synuclein in cerebrospinal fluid.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.734486941.793553768 ◽

2018 ◽

Author(s):

Joseph Jankovic ◽

Arjun Tarakad

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cerebrospinal Fluid ◽

Diagnostic Biomarkers ◽

Disease Focus

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Content of Peripheral Blood T- and B-Cell Subpopulations in Transgenic A53T Mice of Different Age (A Model of Parkinson’s Disease)

Bulletin of Experimental Biology and Medicine ◽

10.1007/s10517-021-05075-w ◽

2021 ◽

Author(s):

G. V. Idova ◽

E. L. Al’perina ◽

M. M. Gevorgyan ◽

M. A. Tikhonova ◽

S. Ya. Zhanaeva

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

B Cell ◽

Peripheral Blood ◽

Cell Subpopulations

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Glucocerebrosidase Activity is Reduced in Cryopreserved Parkinson’s Disease Patient Monocytes and Inversely Correlates with Motor Severity

Journal of Parkinson s Disease ◽

10.3233/jpd-202508 ◽

2021 ◽

pp. 1-9

Author(s):

Laura P. Hughes ◽

Marilia M.M. Pereira ◽

Deborah A. Hammond ◽

John B. Kwok ◽

Glenda M. Halliday ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Rating Scale ◽

Disease Patient ◽

Motor Symptom ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

Classical Monocytes

Background: Reduced activity of lysosomal glucocerebrosidase is found in brain tissue from Parkinson’s disease patients. Glucocerebrosidase is also highly expressed in peripheral blood monocytes where its activity is decreased in Parkinson’s disease patients, even in the absence of GBA mutation. Objective: To measure glucocerebrosidase activity in cryopreserved peripheral blood monocytes from 30 Parkinson’s disease patients and 30 matched controls and identify any clinical correlation with disease severity. Methods: Flow cytometry was used to measure lysosomal glucocerebrosidase activity in total, classical, intermediate, and non-classical monocytes. All participants underwent neurological examination and motor severity was assessed by the Movement Disorders Society Unified Parkinson’s Disease Rating Scale. Results: Glucocerebrosidase activity was significantly reduced in the total and classical monocyte populations from the Parkinson’s disease patients compared to controls. GCase activity in classical monocytes was inversely correlated to motor symptom severity. Conclusion: Significant differences in monocyte glucocerebrosidase activity can be detected in Parkinson’s disease patients using cryopreserved mononuclear cells and monocyte GCase activity correlated with motor features of disease. Being able to use cryopreserved cells will facilitate the larger multi-site trials needed to validate monocyte GCase activity as a Parkinson’s disease biomarker.

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