Journal of Neuroimmune Pharmacology

, Volume 10, Issue 4, pp 561–575 | Cite as

Regulation of the Neurodegenerative Process Associated to Parkinson’s Disease by CD4+ T-cells

  • Hugo González
  • Francisco Contreras
  • Rodrigo Pacheco


Neuroinflammation constitutes a fundamental process involved in the physiopathology of Parkinson’s disease (PD). Microglial cells play a central role in the outcome of neuroinflammation and consequent neurodegeneration of dopaminergic neurons in the substantia nigra. Current evidence indicates that CD4+ T-cells infiltrate the central nervous system (CNS) in PD, where they play a critical role determining the functional phenotype of microglia, thus regulating the progression of the neurodegenerative process. Here, we first analysed the pathogenic role of inflammatory phenotypes and the beneficial role of anti-inflammatory phenotypes of encephalitogenic CD4+ T-cells involved in the physiopathology of PD. Next, we discussed how alterations of neurotransmitter levels observed in the basal ganglia throughout the time course of PD progression could be strongly affecting the behaviour of encephalitogenic CD4+ T-cells and thereby the outcome of the neuroinflammatory process and the consequent neurodegeneration of dopaminergic neurons. Afterward, we integrated the evidence indicating the involvement of an antigen-specific immune response mediated by T-cells and B-cells against CNS-derived self-constituents in PD. Consistent with the involvement of a relevant autoimmune component in PD, we also reviewed the polymorphisms of both, class I and class II major histocompatibility complexes, associated to the risk of PD. Overall, this study gives an overview of how an autoimmune component involved in PD plays a fundamental role in the progression of the neurodegenerative process.


Neuroinflammation CD4+ T-cells Parkinson’s disease Neurotransmitters Autoimmunity 



Alzheimer’s disease


Amyotrophic lateral sclerosis


α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid


Antigen-presenting cells


Blood–brain barrier


Central nervous system


Cerebrospinal fluid




DA receptor n


Experimental autoimmune encephalomyelitis


γ-aminobutyric acid


GABA ionotropic receptors


GABA metabotropic receptors




glu receptors


Granulocyte macrophage-colony stimulating factor


Human leukocyte antigen


interferon γ


interleukin n






Major histocompatibility complex




Multiple sclerosis


Nuclear factor kappa-light-chain-enhancer of activated B cells




Parkinson’s disease


recombination-activating gen 1


RAG1 knockout


Reactive nitrogen species


Reactive oxygen species


Substantia nigra


T-cell receptors


T helper n


Toll like receptors


Transforming growth factor β


Tumor Necrosis Factor α


TNF-α receptor 1





This work was supported by grants 1130271 from the Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT), PFB-16 from the Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) and 10332 from the Michael J. Fox foundation (MJFF).

Compliance with Ethical Standards

This study was funded by grants from the Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT 1130271, to RP), from the Comisión Nacional de Investigación Científica y Tecnológica (PFB-16, to RP) and from the Michael J. Fox foundation (MJFF 10332, to RP). RP is Associate Investigator at Fundación Ciencia & Vida and Associate Professor at Universidad Andres Bello. HG and FC are postdoctoral trainees supervised by RP at the Laboratory of Neuroimmunology of the Fundación Ciencia & Vida. All authors declare that they have no conflicts of interest. This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Hugo González
    • 1
  • Francisco Contreras
    • 1
  • Rodrigo Pacheco
    • 1
    • 2
  1. 1.Laboratory of NeuroimmunologyFundación Ciencia & VidaSantiagoChile
  2. 2.Facultad de Ciencias BiológicasUniversidad Andres BelloSantiagoChile

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