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Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 J+Neuroinflammation 2015 ; 12 (ä): ä Nephropedia Template TP
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Evidence for the involvement of gamma delta T cells in the immune response in Rasmussen encephalitis #MMPMID26186920
Owens GC; Erickson KL; Malone CC; Pan C; Huynh MN; Chang JW; Chirwa T; Vinters HV; Mathern GW; Kruse CA
J Neuroinflammation 2015[]; 12 (ä): ä PMID26186920show ga
Background: Rasmussen encephalitis (RE) is a rare neuroinflammatory disease characterized by intractable seizures and progressive atrophy on one side of the cerebrum. Perivascular cuffing and clusters of T cells in the affected cortical hemisphere are indicative of an active cellular immune response. Methods: Peripheral blood mononuclear cells (PBMCs) and brain-infiltrating lymphocytes (BILs) were isolated from 20 RE surgery specimens by standard methods, and CD3+ T cell populations were analyzed by flow cytometry. Gamma delta T cell receptor spectratyping was carried out by nested PCR of reversed transcribed RNA extracted from RE brain tissue, followed by high resolution capillary electrophoresis. A MiSeq DNA sequencing platform was used to sequence the third complementarity determining region (CDR3) of ?1 chains. Results: CD3+ BILs from all of the RE brain specimens comprised both ?? and ?? T cells. The median ??:?? ratio was 1.9 (range 0.58?5.2) compared with a median ratio of 7.7 (range 2.7?40.8) in peripheral blood from the same patients. The ?? T cells isolated from brain tissue were predominantly CD8+, and the majority of ?? T cells were CD4? 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 13?91 %, and median 47 %; range 14?99 %, respectively). Spectratyping T cell receptor (TCR) V?1-3 chains from 14 of the RE brain tissue 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.