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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02690

Mucosal associated invariant T cell features and TCR repertoire characteristics during the course of Multiple Sclerosis

 Edgar Carnero Contentti1, Mauricio F. Farez2 and  Jorge Correale3*
  • 1Hospital Alemán, Argentina
  • 2Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Argentina
  • 3Neurology, Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Argentina

Objective: To investigate the frequency, phenotype, function and longitudinal repertoire of Mucosal-associated invariant T (MAIT) cells in relapsing remitting (RRMS) and primary progressive MS (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, during 36 months. MAIT cell TCRVβ 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). MAIT cells numbers were also lower during MS relapses. Three months post exacerbation, MAIT cell percentages increased significantly along with clinical recovery. Likewise, we observed inverse correlation between MRI lesions and MAIT cell numbers. In paired samples, MAIT cell percentage was significantly higher in CSF than peripheral blood. Finally, MAIT cells showed limited TCRVβ 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.

Keywords: MAIT cells, Multiple Sclerosis, neuroimmunology, MRI, CSF (cerebrospinal fluid)

Received: 09 Aug 2019; Accepted: 31 Oct 2019.

Copyright: © 2019 Carnero Contentti, Farez and Correale. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Jorge Correale, Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Neurology, Buenos Aires, 1428, Buenos Aires, Argentina,