Background Rasmussen encephalitis (RE) is a rare neuroinflammatory disease characterized by intractable seizures and progressive atrophy on one side of the cerebrum. CD8?. Staining for the early activation marker CD69 showed that a fraction of the and T cells in the BILs were activated (median 42?%; range 13C91?%, and median 47?%; range 14C99?%, respectively). Spectratyping T cell receptor (TCR) V1-3 chains from 14 of the RE brain tissue Reparixin supplier specimens indicated that the T cell repertoire was relatively restricted. Sequencing 1 chain PCR fragments revealed that the same prevalent CDR3 sequences were found in all of the brain specimens. These CDR3 sequences were also detected in brain tissue from 15 focal cortical dysplasia (FCD) cases. Conclusion Neuroinflammation in RE involves both activated and T cells. The presence of T cells with identical TCR 1 chain CDR3 sequences in all of the brain specimens examined suggests that a non-major histocompatibility complex (MHC)-restricted immune response to the same antigen(s) is involved in the etiology of RE. The presence of the same 1 clones in CD brain implies the involvement of a common inflammatory pathway in both diseases. Electronic supplementary material The online version of this article (doi:10.1186/s12974-015-0352-2) contains supplementary material, which is available to authorized users. Keywords: Rasmussen encephalitis, Brain, Inflammation, Focal cortical dysplasia, T cells, Gamma delta T cells, T cell receptor, CDR3 Background Rasmussen encephalitis (RE) is a rare pediatric neurological disease with an estimated incidence in children under the age 18?years of 2C3 per 10 million [1C3]. The acute phase of the disease is characterized by intense uncontrolled partial or generalized seizures, and MRI FLAIR imaging often shows inflammation in one cerebral hemisphere [3]. As the disease progresses, unilateral loss of cerebral tissue leaves the patient with severe hemiparesis and other neurological deficits. Corticosteroids may provide short term benefit but ultimately fail to halt the disease. Early treatment with tacrolimus or intravenous immunoglobulins may stabilize the neurological deterioration, but they do not reverse the intractable epilepsy [2]. An inflammatory response involving T cells and activated microglia confined to the affected hemisphere appears to be the cause of the clinical symptoms. However, what precipitates the immune response is not known. Several types of Herpesviridae have been detected in surgical brain specimens from RE patients; however, to date, there is no consistent evidence for a pathogen that is common to all RE cases [4C7]. Likewise, autoantibodies have been described in RE cases indicative of bHLHb38 an autoimmune disease, but autoantibodies have not been found in all RE cases [8C11]. The observation of polarized granzyme B-containing CD8+ T cells in brain parenchyma in close proximity to neurons and astrocytes has pointed to a role for major histocompatibility complex (MHC) class I-restricted CD8+ cytotoxic T cells in RE [12]. The cytotoxic T cells are likely reacting to foreign or self-antigens displayed by neurons and astrocytes in the affected cerebral hemisphere. Confinement of Reparixin supplier the T cells to one cerebral hemisphere suggests that the initial inflammatory reaction may have been spatially restricted. Such a reaction would have triggered a localized innate immune response by brain resident macrophages (microglia) and could have led to the recruitment of nonresident non-MHC-restricted immune cells, such as natural killer cells and T cells followed by primed MHC-restricted T cells. In the present study, we document for the first time the presence of clonally restricted T Reparixin supplier cells in brain tissue from RE patients, indicating a role for this T cell subtype in the inflammatory response in RE. Methods RE patient cohort and clinical variables Under the University of California, Los Angeles, Institutional Review Board (UCLA IRB) approval (IRB #11-00030), brain tissue and blood were collected Reparixin supplier at surgery as part of UCLAs Reparixin supplier Pediatric Epilepsy Surgery Program. For cases that were not treated at UCLA, tissue and blood were provided to UCLA under the auspices of the UCLA IRB approved Rare Brain Disease Tissue Bank (IRB# 13-001213). All of the patients or their parents or legal guardians provided informed consent for the use of.