Mucosal-Associated Invariant T Cell Features and TCR Repertoire Characteristics During the Course of Multiple Sclerosis.
Front Immunol
; 10: 2690, 2019.
Article
en En
| MEDLINE
| ID: mdl-31824489
Objective: To investigate the frequency, phenotype, function, and longitudinal repertoire of mucosal-associated invariant T (MAIT) cells in relapsing remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS) patients. Methods: Forty-five RRMS patients in remission, 20 RRMS patients experiencing exacerbations, 15 PPMS patients, and 30 healthy controls (HCs) were included in the study. MAIT cells were identified phenotypically as CD3+ TCRγδ- Vα7.2 + CD161high. In 15 patients, MAIT cell number and MRI lesions were evaluated every 6 months, for 36 months. MAIT cell TCRVß repertoire was defined using single-cell cloning and mRNA sequencing. Results: Circulating MAIT cells were significantly reduced in both RRMS and PPMS patients, particularly during exacerbations, compared to healthy subjects. This decrease was accompanied by pro-inflammatory cytokine production (TNF-α, IFN-γ, IL-17, and GM-CSF). Three months post-exacerbation, peripheral blood MAIT cell percentages increased significantly along with clinical recovery. Likewise, we observed inverse correlation between MRI lesions and peripheral blood MAIT cell numbers. In paired samples, MAIT cell percentage was significantly higher in CSF than in peripheral blood, suggesting MAIT cell migration through the blood-brain barrier. Finally, MAIT cells showed limited TCRVß repertoires, in both CSF and peripheral blood, which remained stable over time. Conclusions: MAIT cell levels correlated with MS course both clinically and radiologically, showing marked and sustained oligoclonality. These findings may contribute to a better understanding of pathophysiological phenomena underlying the course of MS, and discovery of MAIT cell inhibitors could pave the way for the development of new therapeutic strategies.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores de Antígenos de Linfocitos T
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Esclerosis Múltiple Crónica Progresiva
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Esclerosis Múltiple Recurrente-Remitente
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Células T Invariantes Asociadas a Mucosa
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Front Immunol
Año:
2019
Tipo del documento:
Article
País de afiliación:
Argentina
Pais de publicación:
Suiza