Tissue resident memory CD8+ T cells are present but not critical for demyelination and neurodegeneration in a mouse model of multiple system atrophy.

Autor:	Corbin-Stein NJ; University of Alabama at Birmingham, Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, Birmingham, AL., Childers GM; University of Alabama at Birmingham, Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, Birmingham, AL., Webster JM; University of Alabama at Birmingham, Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, Birmingham, AL., Zane A; University of Alabama at Birmingham, Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, Birmingham, AL., Yang YT; University of Alabama at Birmingham, Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, Birmingham, AL., Ali MA; University of Alabama at Birmingham, Department of Pathology and Division of Molecular and Cellular Pathology, Birmingham, AL., Sandoval IM; Barrow Neurological Institute, Department of Translational Neuroscience, Phoenix, AZ., Manfredsson FP; Barrow Neurological Institute, Department of Translational Neuroscience, Phoenix, AZ., Kordower JH; ASU-Banner Neurodegenerative Disease Research Center, Biodesign Institute, Arizona State University, Tempe, AZ., Tyrrell DJ; University of Alabama at Birmingham, Department of Pathology and Division of Molecular and Cellular Pathology, Birmingham, AL., Harms AS; University of Alabama at Birmingham, Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, Birmingham, AL.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Jun 03. Date of Electronic Publication: 2024 Jun 03.
DOI:	10.1101/2024.06.02.597035
Abstrakt:	Multiple system atrophy (MSA) is rare, fast progressing, and fatal synucleinopathy with alpha-synuclein (α-syn) inclusions located within oligodendroglia called glial cytoplasmic inclusions (GCI). Along with GCI pathology there is severe demyelination, neurodegeneration, and neuroinflammation. In post-mortem tissue, there is significant infiltration of CD8+ T cells into the brain parenchyma, however their role in disease progression is unknown. To determine the role of CD8+ T cells, a modified AAV, Olig001-SYN, was used to selectively overexpress α-syn in oligodendrocytes modeling MSA in mice. Four weeks post transduction, we observed significant CD8+ T cell infiltration into the striatum of Olig001-SYN transduced mice recapitulating the CD8+ T cell infiltration observed in post-mortem tissue. To understand the role of CD8+ T cells, a CD8 knockout mice were transduced with Olig001-SYN. Six months post transduction into a mouse lacking CD8+ T cells, demyelination and neurodegeneration were unchanged. Four weeks post transduction, neuroinflammation and demyelination were enhanced in CD8 knockout mice compared to wild type controls. Applying unbiased spectral flow cytometry, CD103+, CD69+, CD44+, CXCR6+, CD8+ T cells were identified when α-syn was present in oligodendrocytes, suggesting the presence of tissue resident memory CD8+ T (Trm) cells during MSA disease progression. This study indicates that CD8+ T cells are not critical in driving MSA pathology but are needed to modulate the neuroinflammation and demyelination response. Competing Interests: Competing interests The authors have no competing interests.
Databáze:	MEDLINE
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