MAIT cells are tissue-targeting cells with anti-microbial activity that are implicated as pathogenic in several autoimmune diseases, including adult MS.  Their role remains controversial but pediatric-onset MS offers an opportunity to characterize these cells phenotypically and functionally in early disease onset. Use of the MR1-tetramer is regarded as the most definitive approach to identifying MAIT cells.

To ascertain the identity and evaluate frequencies and pro-inflammatory responses of mucosal associated invariant T cell receptor (MAIT) T cells, using the MR1-tetramer in children with multiple sclerosis (MS), as compared to children with monophasic acquired demyelinating syndromes (monoADS) and healthy controls (HC).

Children with MS, monoADS and HC were recruited as part of the multi-center prospective Canadian Pediatric Demyelinating Disease Study (CPDDS). Peripheral blood was stained for CD161^hiTCR-Vα7.2⁺ CD8⁺ T cells, together with either the MR1 tetramer MR1-5-OP-RU or the negative control tetramer MR1-6-FP (provided by NIH Tetramer Core Facility).

MR1-5-OP-RU tetramer staining correlated strongly with CD8⁺CD161^hiTCR Vα 7.2⁺ T cells (r=0.984, r²= 0.967; p<0.001) and confirmed their identity as MAIT cells in both pediatric MS and controls. Children with MS (n=14) harbored an average of 6.6% CD8⁺ CD161^hiTCR-Vα7.2⁺ MAIT cells within their circulating CD8 T cell pool compared to both HC (n=16; 2.8%) and children with monoADS (n=16; 2.6%). After short-term stimulation, MAIT cells of children with MS exhibited abnormally increased pro-inflammatory responses, as compared to both monoADS and healthy controls.

For the first time we ascertain MR1-tetramer-positive CD8⁺CD161^highTCR-Vα7.2⁺ (MAIT) cells in pediatric MS, reporting not only abnormally increased circulating frequencies, but also a greater functional propensity of these MAIT cells to respond with increased expression of IL-17 and IFNg compared to MAIT cells of both children with monoADS and healthy controls.