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Abstract Details

Mitochondrial Antigen Presentation In Correlation To Parkinson's Disease-like Symptoms.
Movement Disorders
S36 - Movement Disorders: Clinical and Pathologic Characterization of Neurodegenerative Movement Disorders (2:48 PM-3:00 PM)

Dopaminergic neurodegeneration and inflammation are associated with Parkinson's disease (PD). Indeed, T cell infiltration and higher levels of pro-inflammatory cytokines are very often detected in PD patients. Even though the precise causes of dopaminergic neuronal loss in PD are unclear, cellular abnormalities such as the dysfunction of the mitochondria are known to be associated with the disease. Moreover, the involvement of peripheral immunity in PD is gaining increasing interest, as it may act as a major player in the disease. We found that MitAP engagement upon bacterial infection, led to the establishment of autoreactive T cells in PINK1 KO mice, but their direct role in the pathobiology is unknown.

we aimed to decipher the phenotype of these T cells and their direct role in PD.

To directly assess the role of MitAP and mitochondrial specific T cell (mitoT-cells), we generated a new murine model of PD using adoptive transfer of activated mitoT-cells into wild type and PINK1-KO mice. Frequency and level of activation of mitoT-cells was assessed using flow cytometry. We monitored the appearance of PD like symptoms using pole test, grip test and actimetry.

Transfer of mitochondrial specific T cells to mice trigger Parkinson's disease like symptoms as early as day 21 after the transfer. Importantly, these motors symptoms are reversed after L-DOPA administration, strongly accrediting for an affected dopaminergic system. Moreover, immunisation with LPS-treated PINK1-KO DC induced mitoT-cells with the phenotype of Th1, Th17 and Tc17, same as in PD-patients. 

the current study confirm the major role of PINK1 in the regulation of the immune-system and suggest a poor role of this protein in the direct protection of Dopaminergic-neurons. Because these events take place very early compared to motor symptoms, mito-T cells are a valuable early PD biomarker and opens new therapeutic avenues.                      .

Moustafa Badr (CR-CHUM)
Mr. Badr has nothing to disclose.
No disclosure on file
No disclosure on file