{"doi":"10.1101/2024.06.02.597035","title":"Tissue resident memory CD8+ T cells are present but not critical for demyelination and neurodegeneration in a mouse model of multiple system atrophy","abstract":"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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":488564,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9453,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":493946,"name":"Gabrielle Childers","orcid":"0000-0003-1195-4750","position":1,"is_corresponding":false},{"id":1011981,"name":"Jhodi M. Webster","orcid":null,"position":2,"is_corresponding":false},{"id":1011982,"name":"Asta Zane","orcid":null,"position":3,"is_corresponding":false},{"id":1011508,"name":"Yating Yang","orcid":"0000-0001-5207-6742","position":4,"is_corresponding":false},{"id":1037068,"name":"Md Akkas Ali","orcid":"0000-0002-3626-3393","position":5,"is_corresponding":false},{"id":668802,"name":"Ivette M. Sandoval","orcid":null,"position":6,"is_corresponding":false},{"id":495697,"name":"Fredric P. Manfredsson","orcid":"0000-0001-5802-5487","position":7,"is_corresponding":false},{"id":504782,"name":"Jeffrey H. Kordower","orcid":"0000-0001-8629-3294","position":8,"is_corresponding":false},{"id":228518,"name":"Daniel J. Tyrrell","orcid":"0000-0002-0811-6724","position":9,"is_corresponding":false},{"id":279113,"name":"Ashley S. Harms","orcid":"0000-0002-7054-2812","position":10,"is_corresponding":false},{"id":1233083,"name":"Nicole J Corbin-Stein","orcid":"0000-0003-0820-0085","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:08:19.655720Z","pmid":"38895456","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}