JCI：免疫细胞可侵入大脑 增加帕金森氏症患病危险

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法国研究人员日前发现，一种免疫细胞侵入人的大脑后，会转变成“神经元杀手”，从而增加了人患帕金森氏症的危险。这一研究结果将为研制治疗帕金森氏症的特效药提供新思路。

法国居里大学的研究人员艾蒂安·希尔施和斯特凡娜·于诺在最新一期美国《临床检查杂志》上报告说，他们对一些生前患有帕金森氏症的病逝者的尸体进行了解剖，结果在死者的大脑中发现了相当数量的T－CD4淋巴细胞。这种淋巴细胞是一种免疫细胞，具备识别病毒、细菌等病原体并指挥其他免疫细胞攻击病原体的功能，一般情况下不会出现在人的大脑中。研究人员认为，一旦这种淋巴细胞侵入人的大脑，就会杀死神经元细胞，使人患上帕金森氏症。

研究人员随后利用老鼠进行了实验，结果验证了他们的猜想。一旦这种淋巴细胞从患有帕金森氏症的老鼠脑中消失，病鼠的症状就会得到明显的改善。此外，研究人员在病鼠脑中还发现了一种名为FasL分子的存在，T－CD4淋巴细胞正是利用它诱使神经元细胞“自^杀”。

研究人员认为，如果能设法阻止T－CD4淋巴细胞侵入人的大脑，就可以降低人们患帕金森氏症的风险。（生物谷Bioon.com）

生物谷推荐原始出处：

J. Clin. Invest. 119(1): 182-192 (2008). doi:10.1172/JCI36470.

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, H?pital 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, H?pital Lariboisière, Assistance Publique — H?pitaux de Paris, Paris, France.
6Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA.

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.