Evidence for the involvement of gamma delta T cells in the immune response in Rasmussen encephalitis

Autor: Colin C. Malone, Calvin Pan, Thabiso Chirwa, My N. Huynh, Gary W. Mathern, Geoffrey C. Owens, Harry V. Vinters, Julia W. Chang, Kate L. Erickson, Carol A. Kruse
Rok vydání: 2015
Předmět:
Antigens
Differentiation
T-Lymphocyte
Male
Pathology
Receptors
Antigen
T-Cell
alpha-beta
T-Lymphocytes
Gamma delta T cells
Cohort Studies
0302 clinical medicine
Lectins
Receptors
Group I
2.1 Biological and endogenous factors
Aetiology
Child
alpha-beta
0303 health sciences
Immunity
Cellular
biology
C-Type
General Neuroscience
Brain
Receptors
Antigen
T-Cell
gamma-delta
3. Good health
CD
Malformations of Cortical Development
medicine.anatomical_structure
Neurology
Antigen
Differentiation
Child
Preschool
Encephalitis
Female
CDR3
medicine.medical_specialty
Rasmussen encephalitis
T cell
CD3
1.1 Normal biological development and functioning
Clinical Sciences
Immunology
T cells
Major histocompatibility complex
Focal cortical dysplasia
03 medical and health sciences
Cellular and Molecular Neuroscience
Immune system
Underpinning research
Clinical Research
Antigens
CD
medicine
Genetics
Humans
Lectins
C-Type
Antigens
Preschool
Neuroinflammation
030304 developmental biology
Inflammation
gamma-delta
Neurology & Neurosurgery
Epilepsy
Inflammatory and immune system
Research
T-cell receptor
Immunity
Neurosciences
Infant
T-Cell
Complementarity Determining Regions
Brain Disorders
T-Lymphocyte
Malformations of Cortical Development
Group I
biology.protein
Cellular
T cell receptor
030217 neurology & neurosurgery
CD8
Zdroj: Journal of Neuroinflammation
Journal of Neuroinflammation, vol 12, iss 1
Journal of neuroinflammation, vol 12, iss 1
Owens, GC; Erickson, KL; Malone, CC; Pan, C; Huynh, MN; Chang, JW; et al.(2015). Evidence for the involvement of gamma delta T cells in the immune response in Rasmussen encephalitis. Journal of Neuroinflammation, 12(1). doi: 10.1186/s12974-015-0352-2. UCLA: Retrieved from: http://www.escholarship.org/uc/item/3790d805
ISSN: 1742-2094
DOI: 10.1186/s12974-015-0352-2.
Popis: 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 δ1 chains. Results CD3+ BILs from all of the RE brain specimens comprised both αβ and γδ T cells. The median αβ:γδ 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 αβ T cells isolated from brain tissue were predominantly CD8+, and the majority of γδ T cells were CD4− CD8−. Staining for the early activation marker CD69 showed that a fraction of the αβ and γδ T cells in the BILs were activated (median 42 %; range 13–91 %, and median 47 %; range 14–99 %, respectively). Spectratyping T cell receptor (TCR) Vδ1-3 chains from 14 of the RE brain tissue specimens indicated that the γδ T cell repertoire was relatively restricted. Sequencing δ1 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 αβ and γδ T cells. The presence of γδ T cells with identical TCR δ1 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 δ1 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.
Databáze: OpenAIRE
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