CD4+ Regulatory and Effector/Memory T Cell Subsets Profile Motor Dysfunction in Parkinson’s Disease

Saunders, Jessica A. Hutter; Estes, Katherine A.; Kosloski, Lisa M.; Allen, Heather E.; Dempsey, Kathryn; Torres-Russotto, Diego; Meza, Jane L.; Santamaria, Pamela M.; Bertoni, John M.; Murman, Daniel L.; Ali, Hesham; Standaert, David G.; Mosley, R. Lee; Gendelman, Howard E.

doi:10.1007/s11481-012-9402-z

Cited by 273 publications

(247 citation statements)

References 54 publications

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“…Also, impaired abilities of regulatory T cells to suppress effector T cell function were observed in PD patients when T cell phenotype and function were compared with matched controls. These data support the concept that chronic immune stimulation is linked to PD pathobiology and severity (Saunders et al, 2012).…”

Section: Parkinson Diseasesupporting

confidence: 85%

Neuroinflammation: Peripheral and Neurogenic Underlying Processes

Rodríguez‐Ramírez¹,

Adalid‐Peralta²,

Fragoso³

et al. 2015

JCI

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A complex, highly specialized immunomodulatory microenvironment exists in the central nervous system, as a number of protective mechanisms against insults of different kinds have evolved over time to help in maintaining homoeostasis in this compartment.Inflammation in the central nervous system (neuroinflammation) is an elaborate process, triggered in response to challenges of diverse nature. Characterized by increased glial activation (phagocytic phenotype) and the production of pro-inflammatory cytokines, it often leads to blood-brain barrier disruption and leukocyte invasion. While the initial response to an injury involving oxidative and nitrosative stress usually causes acute neuroinflammation, it seldom affects long-term neuronal survival. Chronic neuroinflammation, on the other side, may affect cell survival and brain functions, as observed in several neurodegenerative disorders. Various peripheral and central injuries can alter the homeostasis in the central nervous system, triggering a persistent adaptive inflammatory response that could lead to a vicious circle of neuronal damage.The purpose of this review is to describe the most relevant players in this phenomenon, and to highlight their detrimental role in different neurologic diseases.

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Section: Parkinson Diseasesupporting

confidence: 85%

Neuroinflammation: Peripheral and Neurogenic Underlying Processes

Rodríguez‐Ramírez¹,

Adalid‐Peralta²,

Fragoso³

et al. 2015

JCI

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“…Using flow cytometry analysis, lower total lymphocyte counts were shown in PD patients compared to controls [30,31,32]. The decrease in total lymphocytes was also reported to be due to lower numbers of T (CD3+) and B (CD19+) cells in PD patients.…”

Section: Inflammatory and Immune Mechanisms Involved In Pdmentioning

confidence: 99%

“…The decrease in total lymphocytes was also reported to be due to lower numbers of T (CD3+) and B (CD19+) cells in PD patients. The alterations in CD3+ cells was explained by the reduction in T helper (Th; CD4+) lymphocytes whereas T cytotoxic (CD8+) cells remained unchanged [30,32,33]. Also, the number of ‘naïve' (CD4+CD45RA+) and memory helper (CD4+CD29+) cells was decreased while the number of activated (CD4+CD25+) T cells was markedly increased [30].…”

Section: Inflammatory and Immune Mechanisms Involved In Pdmentioning

confidence: 99%

Depression and Cognitive Impairment in Parkinson's Disease: A Role for Inflammation and Immunomodulation?

Rocha

Reis

Berghe

et al. 2014

Neuroimmunomodulation

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The etiology of Parkinson's disease (PD) is complex and not fully understood, most probably because of the multiplicity of factors involved. Inflammatory and abnormal immune responses have been hypothesized to play a crucial role in PD. Not only in the brain, but also peripherally, inflammation is believed to contribute to the onset and progression of the neurodegenerative process seen in PD. Furthermore, increased inflammatory responses have been described both in the brain and peripheral blood of PD subjects. Although PD is considered a motor disorder, nonmotor symptoms are extremely frequent and disabling. Cognitive impairment and mood alterations are such symptoms that deserve increased attention since on the one hand they can appear even before typical motor disturbances are recognized, and on the other hand they are associated with high morbidity and mortality. A growing body of evidence suggests the existence of a link between inflammatory-immune responses and the occurrence of depression and cognitive impairment in PD patients. However, not all data are equally conclusive and are sometimes even conflicting. The aim of this brief review is to give an overview of the possible role that inflammation and immunomodulation may play in PD together with their putative impact on mood and cognitive alterations. What clearly emerges from this work is the fact that studies performed until now lack standardized and comparable methods to analyze both clinical and biological parameters. It is thus difficult to conclusively link mood and cognitive changes to underlying pathological mechanisms. Additional studies in this direction are warranted to convincingly establish or refute any causative relation.

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“…The balance between effector T cells and Treg activities leads to respective degenerative or protective effects in the brain, depending on defined T-cell polarity and cell phenotype [2,12,[14][15][16][17]. Immune profiles performed in patients with PD support a functional balance between the cells as circulating immunocyte profiles demonstrate increased proinflammatory profiles and decreased Treg function [18]. Such aberrations serve to change the brain's microenvironment, where a proinflammatory dominance ensues.…”

Section: Introductionmentioning

confidence: 99%

Manganese-Enhanced Magnetic Resonance Imaging for Detection of Vasoactive Intestinal Peptide Receptor 2 Agonist Therapy in a Model of Parkinson's Disease

et al. 2016

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Neuroprotective immunity is defined by transformation of T-cell polarity for therapeutic gain. For neurodegenerative disorders and specifically for Parkinson's disease (PD), granulocyte-macrophage colony stimulating factor or vasoactive intestinal peptide receptor 2 (VIPR2) agonists elicit robust anti-inflammatory microglial responses leading to neuronal sparing in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice. While neurotherapeutic potential was demonstrated for PD, there remain inherent limitations in translating these inventions from the laboratory to patients. One obstacle in translating such novel neurotherapeutics centers on the availability of suitable noninvasive methods to track disease progression and therapeutic efficacy. To this end, we developed manganese-enhanced magnetic resonance imaging (MEMRI) assays as a way to track a linkage between glial activation and VIPR2 agonist (LBT-3627)-induced neuroprotective immunity for MPTP-induced nigrostriatal degeneration. Notably, LBT-3627-treated, MPTP-intoxicated mice show reduced MEMRI brain signal intensities. These changes paralleled reduced astrogliosis and resulted in sparing of nigral tyrosine hydroxylase neurons. Most importantly, the data suggest that MEMRI can be developed as a biomarker tool to monitor neurotherapeutic responses that are relevant to common neurodegenerative disorders used to improve disease outcomes.

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CD4+ Regulatory and Effector/Memory T Cell Subsets Profile Motor Dysfunction in Parkinson’s Disease

Cited by 273 publications

References 54 publications

Neuroinflammation: Peripheral and Neurogenic Underlying Processes

Neuroinflammation: Peripheral and Neurogenic Underlying Processes

Depression and Cognitive Impairment in Parkinson's Disease: A Role for Inflammation and Immunomodulation?

Manganese-Enhanced Magnetic Resonance Imaging for Detection of Vasoactive Intestinal Peptide Receptor 2 Agonist Therapy in a Model of Parkinson's Disease

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