Occurrence of T cells in the brain of Alzheimer's disease and other neurological diseases

Togo, Takashi; Akiyama, Haruhiko; Iseki, Eizo; Kondo, Hiromi; Ikeda, Kenji; Kato, Masanori; Oda, Tatsuro; Tsuchiya, Kuniaki; Kosaka, Kenji

doi:10.1016/s0165-5728(01)00496-9

Cited by 399 publications

(313 citation statements)

References 50 publications

Supporting

Mentioning

281

Contrasting

Unclassified

Order By: Relevance

“…Despite this, infiltration of circulating cells has been shown to occur when BBB permeability is increased. Thus T cell infiltration has been found in CNS tissues of patients with Parkinson's disease (Stone et al, 2009) and Alzheimer's disease (Schindowski et al, 2007;Togo et al, 2002) and infiltration of cells has also been reported following ischemic insult and with age (Popescu et al, 2009) and bacterial and viral infections (Stamatovic et al, 2008). In this study, increased BBB permeability was associated with increased expression of IP-10 and MCP-1.…”

Section: Discussionsupporting

confidence: 57%

“…The evidence suggests that there is minimal infiltration of peripheral cells in the healthy brain; this is probably primarily due to the fact that expression of chemotactic agents is low, because migration of cells appears to be controlled mainly by expression of chemokines and adhesion molecules and their receptors. However, there is a marked increase in cell infiltration following trauma (Shichita et al, 2009) and in neurodegenerative conditions (Stone et al, 2009;Togo et al, 2002) when the blood-brain barrier (BBB) is breached and when expression of chemotactic agents is increased.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The age-related deficit in LTP is associated with changes in perfusion and blood-brain barrier permeability

Blau¹,

Cowley²,

O'Sullivan³

et al. 2012

Neurobiology of Aging

View full text Add to dashboard Cite

In view of the increase in the aging population and the unavoidable parallel increase in the incidence of age-related neurodegenerative diseases, a key challenge in neuroscience is the identification of clinical signatures which change with age and impact on neuronal and cognitive function. Early diagnosis offers the possibility of early therapeutic intervention, thus magnetic resonance imaging (MRI) is potentially a powerful diagnostic tool. We evaluated age-related changes in relaxometry, blood flow, and blood-brain barrier (BBB) permeability in the rat by magnetic resonance imaging and assessed these changes in the context of the age-related decrease in synaptic plasticity. We report that T2 relaxation time was decreased with age; this was coupled with a decrease in gray matter perfusion, suggesting that the observed microglial activation, as identified by increased expression of CD11b, MHCII, and CD68 by immunohistochemistry, flow cytometry, or polymerase chain reaction (PCR), might be a downstream consequence of these changes. Increased permeability of the blood-brain barrier was observed in the perivascular area and the hippocampus of aged, compared with young, rats. Similarly there was an age-related increase in CD45-positive cells by flow cytometry, which are most likely infiltrating macrophages, with a parallel increase in the messenger mRNA expression of chemokines IP-10 and MCP-1. These combined changes may contribute to the deficit in long-term potentiation (LTP) in perforant path-granule cell synapses of aged animals.

show abstract

Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

The age-related deficit in LTP is associated with changes in perfusion and blood-brain barrier permeability

Blau¹,

Cowley²,

O'Sullivan³

et al. 2012

Neurobiology of Aging

View full text Add to dashboard Cite

show abstract

“…In previous work, we found that in analogy to the therapeutic effect of amyloid-␤ immunization in a mouse model of Alzheimer's disease (3), immunization with prion protein peptide reduced the PrP Sc content of a transplanted neuroblastoma (38). Moreover, recent publications have described inflammatory cells and molecules in several neurodegenerative diseases, including Parkinson's (39), Alzheimer's (40,41), and experimental prion disease (42). These findings raise the possibility that Ag-specific T or B cells might influence the natural history of these neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 95%

Autoimmune Encephalomyelitis and Uveitis Induced by T Cell Immunity to Self β-Synuclein

Mor

Quintana

Mimran

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

β-synuclein is a neuronal protein that accumulates in the plaques that characterize neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. It has been proposed that immunization to peptides of plaque-forming proteins might be used therapeutically to help dissociate pathogenic plaques in the brain. We now report that immunization of Lewis rats with a peptide from β-synuclein resulted in acute paralytic encephalomyelitis and uveitis. T cell lines and clones reactive to the peptide adoptively transferred the disease to naive rats. Immunoblotting revealed the presence of β-synuclein in heavy myelin, indicating that the expression of β-synuclein is not confined to neurons. These results add β-synuclein to the roster of encephalitogenic self Ags, point out the potential danger of therapeutic autoimmunization to β-synuclein, and alert us to the unsuspected possibility that autoimmunity to β-synuclein might play an inflammatory role in the pathogenesis of neurodegeneration.

show abstract

“…It was suggested that the inflammation occurring in the brain of AD patients has systemic parallels, and there are many reports supporting the concept that AD is a systemic inflammatory disease (Britschgi and WyssCoray, 2007). A number of reports also show that more T-cells are activated in AD patients than age-matched controls, and that these cells are present both in the periphery and as infiltrates in the brain (Togo et al, 2002;Town et al, 2005;Li et al, 2009). In vitro studies have shown that Aβ induces the production of chemokines such as MIP-1α, RANTES and MCP-1 by PBMCs of AD patients and the expression of CCR5 on brain endothelial cells; this might enhance the migration of peripheral T cells across the blood brain barrier (BBB) (Li et al, 2009;Reale et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Immune profiling of Alzheimer patients

Pellicanò

Larbi

Goldeck

et al. 2012

Journal of Neuroimmunology

129

View full text Add to dashboard Cite

Alzheimer's disease (AD) is characterized by extracellular senile plaques in the brain, containing amyloid-β peptide (Aβ). We identify immunological differences between AD patients and age-matched controls greater than those related to age itself. The biggest differences were in the CD4+ rather than the CD8+ T cell compartment resulting in lower proportions of naïve cells, more late-differentiated cells and higher percentages of activated CD4+CD25+ T cells without a Treg phenotype in AD patients. Changes to CD4+ cells might be the result of chronic stimulation by Aβ present in the blood. These findings have implications for diagnosis and understanding the aetiology of the disease.

show abstract

Occurrence of T cells in the brain of Alzheimer's disease and other neurological diseases

Cited by 399 publications

References 50 publications

The age-related deficit in LTP is associated with changes in perfusion and blood-brain barrier permeability

The age-related deficit in LTP is associated with changes in perfusion and blood-brain barrier permeability

Autoimmune Encephalomyelitis and Uveitis Induced by T Cell Immunity to Self β-Synuclein

Immune profiling of Alzheimer patients

Contact Info

Product

Resources

About