title: Evidence for Resident Memory T Cells in Rasmussen Encephalitis.
abstract: Rasmussen encephalitis (RE) is a rare pediatric neuroinflammatory disease of unknown etiology characterized by intractable seizures, and progressive atrophy usually confined to one cerebral hemisphere. Surgical removal or disconnection of the affected cerebral hemisphere is currently the only intervention that effectively stops the seizures. Histopathological evaluation of resected brain tissue has shown that activated brain resident macrophages (microglia) and infiltrating T cells are involved in the inflammatory reaction. Here, we report that T cells isolated from seven RE brain surgery specimens express the resident memory T cell (TRM) marker CD103. CD103 was expressed by >50% of CD8(+) αβ T cells and γδ T cells irrespective of the length of time from seizure onset to surgery, which ranged from 0.3 to 8.4 years. Only ~10% of CD4(+) αβ were CD103(+), which was consistent with the observation that few CD4(+) T cells are found in RE brain parenchyma. Clusters of T cells in brain parenchyma, which are a characteristic of RE histopathology, stained for CD103. Less than 10% of T cells isolated from brain specimens from eight surgical cases of focal cortical dysplasia (FCD), a condition that is also characterized by intractable seizures, were CD103(+). In contrast to the RE cases, the percent of CD103(+) T cells increased with the length of time from seizure onset to surgery. In sections of brain tissue from the FCD cases, T cells were predominantly found around blood vessels, and did not stain for CD103. The presence of significant numbers of TRM cells in RE brain irrespective of the length of time between clinical presentation and surgical intervention supports the conclusion that a cellular immune response to an as yet unidentified antigen(s) occurs at an early stage of the disease. Reactivated TRM cells may contribute to disease progression.
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at UCLA , Los Angeles, CA , USA.
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Owens
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Julia W
authors.initials: JW
authors.lastname: Chang
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at UCLA , Los Angeles, CA , USA.
authors.forename: My N
authors.initials: MN
authors.lastname: Huynh
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at UCLA , Los Angeles, CA , USA.
authors.forename: Thabiso
authors.initials: T
authors.lastname: Chirwa
authors.affiliation: Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Harry V
authors.initials: HV
authors.lastname: Vinters
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Mattel Children's Hospital, Los Angeles, CA, USA.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Mathern
keywords: Rasmussen encephalitis; alpha beta T cells; focal cortical dysplasia; gamma delta T cells; resident memory T cells