Dual destructive and protective roles of adaptive immunity in neurodegenerative disorders

Kristi M. Anderson, Katherine E. Olson, Katherine A. Estes, Ken Flanagan, Howard Eliot Gendelman, R Lee Mosley

Research output: Contribution to journalReview article

31 Citations (Scopus)

Abstract

Inappropriate T cell responses in the central nervous system (CNS) affect the pathogenesis of a broad range of neuroinflammatory and neurodegenerative disorders that include, but are not limited to, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease and Parkinson's disease. On the one hand immune responses can exacerbate neurotoxic responses. while on the other hand, they can lead to neuroprotective outcomes. The temporal and spatial mechanisms by which these immune responses occur and are regulated in the setting of active disease have gained significant recent attention. Spatially, immune responses that affect neurodegeneration may occur within or outside the CNS. Migration of antigen-specific CD4+ T cells from the periphery to the CNS and consequent immune cell interactions with resident glial cells affect neuroinflammation and neuronal survival. The destructive or protective mechanisms of these interactions are linked to the relative numerical and functional dominance of effector or regulatory T cells. Temporally, immune responses at disease onset or during progression may exhibit a differential balance of immune responses in the periphery and within the CNS. Immune responses with predominate T cell subtypes may differentially manifest migratory, regulatory and effector functions when triggered by endogenous misfolded and aggregated proteins and cell-specific stimuli. The final result is altered glial and neuronal behaviors that influence the disease course. Thus, discovery of neurodestructive and neuroprotective immune mechanisms will permit potential new therapeutic pathways that affect neuronal survival and slow disease progression.

Original languageEnglish (US)
Article number25
JournalTranslational Neurodegeneration
Volume3
Issue number1
DOIs
StatePublished - Nov 13 2014

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Adaptive Immunity
Neurodegenerative Diseases
Central Nervous System
T-Lymphocytes
Neuroglia
CD4 Antigens
Amyotrophic Lateral Sclerosis
Regulatory T-Lymphocytes
Cell Communication
Multiple Sclerosis
Parkinson Disease
Disease Progression
Alzheimer Disease
Proteins
Therapeutics

Keywords

  • Effector T cell
  • MCAM
  • MPTP
  • Migration
  • Neurodegeneration
  • Neuroinflammation
  • Neuroprotection
  • Regulatory T cell

ASJC Scopus subject areas

  • Clinical Neurology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Dual destructive and protective roles of adaptive immunity in neurodegenerative disorders. / Anderson, Kristi M.; Olson, Katherine E.; Estes, Katherine A.; Flanagan, Ken; Gendelman, Howard Eliot; Mosley, R Lee.

In: Translational Neurodegeneration, Vol. 3, No. 1, 25, 13.11.2014.

Research output: Contribution to journalReview article

Anderson, Kristi M. ; Olson, Katherine E. ; Estes, Katherine A. ; Flanagan, Ken ; Gendelman, Howard Eliot ; Mosley, R Lee. / Dual destructive and protective roles of adaptive immunity in neurodegenerative disorders. In: Translational Neurodegeneration. 2014 ; Vol. 3, No. 1.
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