Alterations of T cell subsets in ALS: a systemic immune activation?

Rentzos, Michael; Evangelopoulos, Maria-Eleftheria; Sereti, Eleni; Zouvelou, Vasiliki; Marmara, S.; Alexakis, Theodoros; Evdokimidis, Ioannis

doi:10.1111/j.1600-0404.2011.01528.x

Cited by 111 publications

(97 citation statements)

References 33 publications

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“…Henkel et al [133] demonstrated that in patients with rapidly progressing clinical states, an inverse correlation was seen between Treg numbers in the blood and leukocyte levels of FoxP3, a transcription factor required for Treg suppressive function [134]. In a second cohort of patients with ALS, the decreased cell numbers and decreased FoxP3 expression were 80 % sensitive in predicting rapid progression in patients with ALS.…”

Section: Neuroinflammation In Patients With Als: Tregsmentioning

confidence: 99%

Protective and Toxic Neuroinflammation in Amyotrophic Lateral Sclerosis

et al. 2015

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Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous disorder characterized by loss of motor neurons, resulting in paralysis and death. Multiple mechanisms of motor neuron injury have been implicated based upon the more than 20 different genetic causes of familial ALS. These inherited mutations compromise diverse motor neuron pathways leading to cell-autonomous injury. In the ALS transgenic mouse models, however, motor neurons do not die alone. Cell death is noncell-autonomous dependent upon a well orchestrated dialogue between motor neurons and surrounding glia and adaptive immune cells. The pathogenesis of ALS consists of 2 stages: an early neuroprotective stage and a later neurotoxic stage. During early phases of disease progression, the immune system is protective with glia and T cells, especially M2 macrophages/microglia, and T helper 2 cells and regulatory T cells, providing anti-inflammatory factors that sustain motor neuron viability. As the disease progresses and motor neuron injury accelerates, a second rapidly progressing phase develops, characterized by M1 macrophages/microglia, and proinflammatory T cells. In rapidly progressing ALS patients, as in transgenic mice, neuroprotective regulatory T cells are significantly decreased and neurotoxicity predominates. Our own therapeutic efforts are focused on modulating these neuroinflammatory pathways. This review will focus on the cellular players involved in neuroinflammation in ALS and current therapeutic strategies to enhance neuroprotection and suppress neurotoxicity with the goal of arresting the progressive and devastating nature of ALS.

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Section: Neuroinflammation In Patients With Als: Tregsmentioning

confidence: 99%

Protective and Toxic Neuroinflammation in Amyotrophic Lateral Sclerosis

et al. 2015

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“…Low T cells numbers and decreased proliferative capacity in T cells are found in the blood of ALS patients (Holmoy et al, 2008). As concerned CD8+ and natural killer T cells, they were found increased in ALS patients compared to control cohort (Rentzos et al, 2011). Interestingly, ALS patients showed a reduction of CD4+/CD25+ regulatory T cells that are known to interact with the local microglia, reinforcing the hypothesis of the involvement of the adaptive immune system associated with neuroinflammatory process in ALS (Mantovani et al, 2009).…”

Section: Adaptive Immune Systemmentioning

confidence: 50%

The Role of TNF-Alpha in ALS: New Hypotheses for Future Therapeutic Approaches

Cereda¹,

Gagliardi²,

Cova³

et al. 2012

Amyotrophic Lateral Sclerosis

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“…An in-depth autopsy of six ALS patients reveals an enrichment of T-cell receptor Vβ2 positive T cells in the spinal cord and CSF, suggesting an antigen-driven T cell selection [150]. Finally, ALS patients with a more rapidly progressing pathology show decreased numbers of regulatory T lymphocytes (Tregs), suggesting that the numbers of Tregs are inversely correlated with disease progression [144,151]. Tregs secrete anti-inflammatory cytokines such as IL-4, IL-10 and transforming growth factor beta (TGF-β) as well as the neurotrophic growth factors glial-derived neurotrophic factor (GDNF) and BDNF.…”

Section: Pathological Phenotype Of the Immune System In Alsmentioning

confidence: 98%

“…Presence of a systemic immune activation is suggested by abnormalities observed in the blood and CSF of ALS patients such as increased numbers of circulating lymphocytes (CD4+ helper T cells, CD8+ cytotoxic T lymphocytes (CTL) and natural killer (NK) cells), increased expression of MHC class II molecules on monocytes as well as higher levels of inflammatory chemokines and cytokines (regulated on activation normal T cell expressed and secreted (RANTES), monocyte chemotactic protein (MCP-1), IL-12, IL-15, IL-17 and IL-23) [142][143][144][145][146]. Further, post-mortem studies of brain and spinal cord from ALS patients show that the activation and proliferation of microglia is associated with an infiltration of activated macrophages, mast cells and T lymphocytes which are found in close proximity to degenerating tissues [147][148][149].…”

Section: Pathological Phenotype Of the Immune System In Alsmentioning

confidence: 99%

“…Tregs are also able to dampen a Th1 pro-inflammatory response and attenuate toxic microglial responses. Contribution of the innate immune system is also suggested by the presence of immunoglobulins and complement deposition as well as a significant increase of NK cells in the blood of ALS patients [87,144,152]. While these investigations of ALS samples and tissues do not assess the contributory role of the immune system to the disease pathogenesis, they do highlight its active presence.…”

Section: Pathological Phenotype Of the Immune System In Alsmentioning

confidence: 99%

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