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Disease management involves anti-seizure medications and immunotherapy, although surgical resection remains the only effective treatment option to achieve seizure freedom. The presence of clonally expanded resident memory T cells in brain tissue removed to control seizures suggests the involvement of an autoimmune response in the etiology of the disease. Blocks of fresh brain tissue were obtained from three RE surgery cases (ages 5, 8, and 26\u00a0years at the time of surgery) and immune cells were isolated. Single cell RNA sequencing was used to define the types of immune cells present in the affected brain tissue and potential crosstalk between them, along with multiplex immunofluorescence immunostaining of sections from the same specimens. We matched T cell receptor sequences to T cell phenotypes and used ViralTrack software to search for evidence of activation of latent viruses in the immune cells. The immune cells isolated from the three RE cases comprised primarily activated microglia and resident memory CD8 T cells with fewer CD4 T cells, NK cells and monocyte-derived macrophages and dendritic cells. The majority of CD8 T cells expressed killer cell lectin-like receptors, and a virus responsive gene signature that included XCL1, TNFRSF9 and CRTAM, but also the exhaustion markers LAG-3 and TIM-3. Microglia expressed transcripts found in disease-associated microglia and transcripts associated with NLRP3 inflammasomes. We found no evidence for active latent viruses; however, we found endogenous HERV-K retrovirus sequences that were transcribed from multiple provirus insertion sites.<\/jats:p>","DOI":"10.1038\/s41598-026-51295-3","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T14:25:20Z","timestamp":1778682320000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immune landscape of the affected brain in Rasmussen encephalitis"],"prefix":"10.1038","volume":"16","author":[{"given":"Giovanni","family":"Quinones-Valdez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia W.","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shino D.","family":"Magaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry V.","family":"Vinters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Salamon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony C.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aria","family":"Fallah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey C.","family":"Owens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"51295_CR1","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1093\/brain\/awh415","volume":"128","author":"CG Bien","year":"2005","unstructured":"Bien, C. 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