Journal of Neuroimmune Pharmacology

, Volume 10, Issue 4, pp 561–575

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

  • Hugo González
  • Francisco Contreras
  • Rodrigo Pacheco
INVITED REVIEW

DOI: 10.1007/s11481-015-9618-9

Cite this article as:
González, H., Contreras, F. & Pacheco, R. J Neuroimmune Pharmacol (2015) 10: 561. doi:10.1007/s11481-015-9618-9

Abstract

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.

Keywords

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

Abbreviations

AD

Alzheimer’s disease

ALS

Amyotrophic lateral sclerosis

AMPA

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

APCs

Antigen-presenting cells

BBB

Blood–brain barrier

CNS

Central nervous system

CSF

Cerebrospinal fluid

DA

dopamine

DnR

DA receptor n

EAE

Experimental autoimmune encephalomyelitis

GABA

γ-aminobutyric acid

GABAARs

GABA ionotropic receptors

GABABRs

GABA metabotropic receptors

glu

glutamate

GluR

glu receptors

GM-CSF

Granulocyte macrophage-colony stimulating factor

HLA

Human leukocyte antigen

IFN-γ

interferon γ

IL-n

interleukin n

L-DOPA

L-3,4-dihydroxyphenylalanine

LPS

Lipopolysaccharide

MHC

Major histocompatibility complex

MPTP

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

MS

Multiple sclerosis

NF-κB

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

NMDA

N-methyl-D-aspartate

PD

Parkinson’s disease

RAG1

recombination-activating gen 1

RAG1KO

RAG1 knockout

RNS

Reactive nitrogen species

ROS

Reactive oxygen species

SN

Substantia nigra

TCRs

T-cell receptors

Thn

T helper n

TLRs

Toll like receptors

TGF-β

Transforming growth factor β

TNF-α

Tumor Necrosis Factor α

TNFR1

TNF-α receptor 1

6-OHDA

6-hydroxidopamine.

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