P2‐507: MHC‐independent genetic factors control the magnitude of CD4+ T cell responses to amyloid‐beta peptide in mice through regulatory T cell‐mediated inhibition

Toly-Ndour, Cécile; Lui, Gabrielle; Nunes, Maria Manuel; Chaigneau, Thomas; Bruley-Rosset, M.; Aucouturier, Pièrre; Dorothée, Guillaume

doi:10.1016/j.jalz.2011.05.1378

Cited by 2 publications

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“…In mice, Ab immunogenicity markedly differs between strains; for example, Ab is highly immunogenic in NOD and SJL mice, which have a dominant T-cell epitope between residues 10 and 24 of Ab, whereas the peptide evokes only weak T-cell responses in C57BL/6 mice in which the epitope is between residues 16 and 30. [30][31][32] NOD congenic mice bearing the I-A b class II allele also fail to elicit a strong T-cell response, suggesting that the low immunogenicity of Ab 16-30 in C57BL/6 mice is primarily a result of a low-affinity epitope selected by the I-A b MHC class II. However, both C57BL/6 and B6.H-2 s congenic mice, but not SJL mice, exhibit enhanced Ab-specific T-cell responses upon the depletion of regulatory T (Treg) cells, suggesting that under certain genetic backgrounds, Treg cells can significantly affect Ab immunogenicity.…”

Section: Main Bodymentioning

confidence: 99%

“…However, both C57BL/6 and B6.H-2 s congenic mice, but not SJL mice, exhibit enhanced Ab-specific T-cell responses upon the depletion of regulatory T (Treg) cells, suggesting that under certain genetic backgrounds, Treg cells can significantly affect Ab immunogenicity. 31 As no differences in thymic expression of APP are observed between C57BL/6 and SJL mice, the mechanism behind the effect of Treg cells on Ab immunogenicity in C57BL/ 6 mice and the reason it is not effective in the more Abimmunogenic SJL mice are yet to be revealed.…”

Section: Main Bodymentioning

confidence: 99%

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CD4 T cells in immunity and immunotherapy of Alzheimer's disease

2013

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SummaryAlzheimer's disease (AD) is the most common form of dementia, with prevalence progressively increasing with aging. Pathological hallmarks of the disease include accumulation of amyloid b-protein (Ab) peptides and neurofibrillary tangles in the brain associated with glial activation and synaptotoxicity. In addition, AD involves peripheral and brain endogenous inflammatory processes that appear to enhance disease progression. More than a decade ago a new therapeutic paradigm emerged for AD, namely the activation of the adaptive immune system directly against the self-peptide Ab, aimed at lowering its accumulation in the brain. This was the first time that a brain peptide was used to vaccinate human subjects in a manner similar to classic viral or bacterial vaccines. The vaccination approach has taken several forms, from initially active to passive and then back to modified active vaccines. As the first two approaches to date failed to show sufficient efficacy, the last is presently being evaluated in ongoing clinical trials. The present review summarizes the immunogenic characteristics of Ab in humans and mice and discusses past, present and future Ab-based immunotherapeutic approaches for AD. We emphasize potential pathogenic and beneficial roles of CD4 T cells in light of the pathogenesis and the general decline in T-cell responsiveness evident in the disease.

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Section: Main Bodymentioning

confidence: 99%

Section: Main Bodymentioning

confidence: 99%

CD4 T cells in immunity and immunotherapy of Alzheimer's disease

2013

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“…Significant infiltration of immune cells, including macrophages, occurs when there is evidence of neuroinflammation, for example, in aged animals and animal models of AD (Becher et al, 2017; Blau et al, 2012; Korin et al, 2017; McManus et al, 2014; Mrdjen et al, 2018; Toly-Ndour et al, 2011; Wolfe et al, 2018). The presence of NK cells (Kelly et al, 2013) and neutrophils (Minogue et al, 2014) has also been reported in the brain of APP/PS1 mice, and a correlation between blood–brain barrier (BBB) permeability and infiltrating cells has been identified (Blau et al, 2012; Denieffe et al, 2013; Kelly et al, 2013; Minogue et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…In the 3xTg-AD transgenic mouse model, adoptive transfer of Tregs ameliorated cognitive decline, reduced Aβ burden and reduced the expression of proinflammatory cytokines and increased the expression of IL-10 in splenocytes (Baek et al, 2016). However, it has been reported that Tregs can modulate Aβ-induced CD4 + T-cell responses in APP/PS1 mice, and this may also impact the observed neuroinflammation (Toly-Ndour et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

The role of the immune system in driving neuroinflammation

Chasaide

Lynch

2020

Brain and Neuroscience Advances

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Neuroinflammation is now recognised as an important contributory factor in the progression of Alzheimer’s disease and probably also in the early stages of the disease. It is likely that this derives largely from aberrant activation of microglia, the resident mononuclear phagocytes of the brain. These cells are responsible for physiological immune surveillance and clearance of pathogens in the central nervous system, but evidence indicates that in Alzheimer’s disease, microglial function is compromised, and this contributes to the pathology. It is unclear what factors cause the inappropriate activation of the microglia in Alzheimer’s disease, but one contributor may be infiltrating peripheral immune cells and these include macrophages and T cells. It has been suggested that both cell types modulate the phenotype of microglia, highlighting the importance of crosstalk between the innate and adaptive immune system in Alzheimer’s disease. This review outlines our current knowledge of how cells of the peripheral immune system, specifically macrophages and T cells, may modulate microglial phenotype in the context of Alzheimer’s disease and considers the impact on their function, especially phagocytic capacity.

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P2‐507: MHC‐independent genetic factors control the magnitude of CD4+ T cell responses to amyloid‐beta peptide in mice through regulatory T cell‐mediated inhibition

Cited by 2 publications

References 0 publications

CD4 T cells in immunity and immunotherapy of Alzheimer's disease

CD4 T cells in immunity and immunotherapy of Alzheimer's disease

The role of the immune system in driving neuroinflammation

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