| Parkinson disease may be an immune system dysfunction! |
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Hi team members, this is another reason to keep your immune system balanced and smart. Be blessed. Mike
Research Article
Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease
Vanessa Brochard1,2, Béhazine Combadière3, Annick Prigent1,2, Yasmina Laouar4, Aline Perrin1,2, Virginie Beray-Berthat1,2, Olivia Bonduelle3, Daniel Alvarez-Fischer1,2, Jacques Callebert5, Jean-Marie Launay5, Charles Duyckaerts1,2, Richard A. Flavell4,6, Etienne C. Hirsch1,2 and Stéphane Hunot1,2
1INSERM, UMR S679, Experimental Neurology and Therapeutics, Hôpital de la Salpêtrière, Paris, France.
2Université Pierre et Marie Curie — Paris 06, UMR S679, Paris, France.
3INSERM U543, Université Pierre et Marie Curie — Paris 06, Paris, France.
4Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
5CR Claude Bernard, IFR6, Service de Biochimie, Hôpital Lariboisière, Assistance Publique — Hôpitaux de Paris, Paris, France.
6Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA.
Address correspondence to: Stéphane Hunot or Etienne C. Hirsch, INSERM UMR 679, Hôpital de la Salpêtrière, 47 Bd de l'Hôpital, 75013 Paris, France. Phone: 33-14-21-62-172; Fax: 33-14-42-43-658; E-mail: stephane.hunot@upmc.fr (S. Hunot). Phone: 33-14-21-62-202; Fax: 33-14-42-43-658; E-mail: etienne.hirsch@upmc.fr (E.C. Hirsch).
First published December 22, 2008
Received for publication June 11, 2008, and accepted in revised form November 12, 2008.
Parkinson disease (PD) is a neurodegenerative disorder characterized by a loss of dopamine-containing neurons. Mounting evidence suggests that dopaminergic cell death is influenced by the innate immune system. However, the pathogenic role of the adaptive immune system in PD remains enigmatic. Here we showed that CD8+ and CD4+ T cells but not B cells had invaded the brain in both postmortem human PD specimens and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD during the course of neuronal degeneration. We further demonstrated that MPTP-induced dopaminergic cell death was markedly attenuated in the absence of mature T lymphocytes in 2 different immunodeficient mouse strains (Rag1–/– and Tcrb–/– mice). Importantly, similar attenuation of MPTP-induced dopaminergic cell death was seen in mice lacking CD4 as well as in Rag1–/– mice reconstituted with FasL-deficient splenocytes. However, mice lacking CD8 and Rag1–/– mice reconstituted with IFN-γ–deficient splenocytes were not protected. These data indicate that T cell–mediated dopaminergic toxicity is almost exclusively arbitrated by CD4+ T cells and requires the expression of FasL but not IFNγ. Further, our data may provide a rationale for targeting the adaptive arm of the immune system as a therapeutic strategy in PD. |
ref:http://www.professionalnetworkers.com/forum/viewtopic.php?t=13115
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