Scientists in France and the US discovered that a type of immune system cell may facilitate the development of Parkinson’s Disease and that targetting part of the immune system with drugs could be a new way to treat the disease.
The study, which is published in the Journal of Clinical Investigation was the work of lead author Vanessa Brochard of the Experimental Neurology and Therapeutics department at the INSERM medical research institute at the Hôpital de la Salpêtrière, Paris, France, and colleagues from other research centres in France and the US. Brochard also works at the Université Pierre et Marie Curie in Paris.
Parkinson’s disease is a neurodegenerative disorder that affects the motor system. Symptoms include tremor, slowed movements, rigidity and impaired balance and coordination caused by a reduction in dopamine producing cells in the brain.
Scientists already knew that Parkinson’s disease was accompanied by changes to dopamine and non-dopamine brain cells and their signalling pathways, plus inflammatory changes to microglia (innate immune cells in the central nervous system), and infiltration of T lymphocytes (cells of the adaptive immune system) into the brain. However, until this study, it was assumed that some of these changes (the microglial and T cell infiltration) were the result of injury rather influencers of primary events.
This study suggests otherwise and provides compelling evidence that “both activated microglia and T lymphocytes make a significant contribution to neurodegeneration”, wrote Stanley H. Appel of Department of Neurology, Methodist Neurological Institute, Houston, Texas, USA, in an accompanying commentary. Even if these events are not the primary cause of Parkinson’s Disease, at the very least they worsen the inflammatory process and help extensive damage to develop from a small population of stressed dopamine cells, said Appel.
In their study, Brochard and colleagues used postmortem evidence of human patients to show that CD8+ and CD4+ T cells but not B cells had invaded their brains. They then used mice that had been given a neurotoxin to induce symptoms of Parkinson’s (the MPTP mouse model) to show that it was almost exclusively the CD4+ T cells that arbitrated the accelerated death of dopamine cells but this only happened when the FasL cell death triggering protein was expressed and not when the Ifn-γ inflammation cytokine was expressed.
The study gives further evidence that the immune system can both protect and attack the brain. Although the study opens the door to developing new treatments for Parkinson’s Disease that target the immune system, there is still a lot of work to be done. Much of the evidence relies on what happens in mice, which does not necessarily translate to humans, and it is by no means clear at which stage of inflammation development intervention should occur. Another important step will be to identify which of the subpopulations of CD4+ T cells in the human immune system are responsible for killing dopamine cells and which protect them.
As Appel explained, Brochard and colleagues went some way toward this by showing that the immune system T helper cells Th1 and Th17 may be useful targets for minimizing hostile environments for brain cells, either by targetting them directly, or by suppressing some of the signalling pathways that control them.
“Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease.”
Vanessa Brochard, Béhazine Combadière, Annick Prigent, Yasmina Laouar, Aline Perrin, Virginie Beray-Berthat, Olivia Bonduelle, Daniel Alvarez- Fischer, Jacques Callebert, Jean-Marie Launay, Charles Duyckaerts, Richard A. Flavell, Etienne C. Hirsch, Stéphane Hunot.
J. Clin. Invest. Published online December 22, 2008.
doi:10.1172/JCI36470
“CD4+ T cells mediate cytotoxicity in neurodegenerative diseases.”
Stanley H. Appel
J. Clin. Invest. Published online December 22, 2008.
doi:10.1172/JCI38096
Sources: JCI.
Written by: Catharine Paddock, PhD