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Abstract Details

Abnormal Frequency and Function of MR1-defined MAIT cells in Pediatric Multiple Sclerosis
Multiple Sclerosis
S55 - MS Basic Science (4:36 PM-4:47 PM)
007

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 CD161hiTCR-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+CD161hiTCR 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+ CD161hiTCR-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+CD161highTCR-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.

Authors/Disclosures
Ina Mexhitaj, PhD (Sanofi)
PRESENTER
No disclosure on file
No disclosure on file
Rui Li (McGill University) No disclosure on file
Julia O'Mahony (The Hospital for Sick Children) Ms. O'Mahony has nothing to disclose.
No disclosure on file
No disclosure on file
Craig S. Moore, PhD (Memorial University of Newfoundland) Dr. Moore has nothing to disclose.
Trina Johnson, MD No disclosure on file
Dessa Sadovnick, PhD (VCHA-UBC Hospital) No disclosure on file
No disclosure on file
Douglas L. Arnold, MD, FAAN (Montreal Neurological Institute, McGill Univ) Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Frequency Therapeutics. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Xfacto communications. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Find therapeutics. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Idorsia. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kiniksa. Dr. Arnold has stock in NeuroRx.
Bruno Gran, MD, PhD (Nottingham University Hospitals) Dr. Gran has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gilead. Dr. Gran has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche UK. Dr. Gran has received publishing royalties from a publication relating to health care.
E. Ann Yeh, MD, MA, FRCPC (Hosptial for Sick Children) Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for PRIME. Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Yeh has received research support from Biogen. The institution of Dr. Yeh has received research support from Stem Cell Network. The institution of Dr. Yeh has received research support from CIHR. The institution of Dr. Yeh has received research support from Ontario Institute for Regenerative Medicine. The institution of Dr. Yeh has received research support from National MS Society. The institution of Dr. Yeh has received research support from NIH. The institution of Dr. Yeh has received research support from SickKids Foundation. The institution of Dr. Yeh has received research support from CMSC. The institution of Dr. Yeh has received research support from MSSC.
Ruth-Ann Marrie, MD, PhD (University of Manitoba) The institution of Dr. Marrie has received research support from CIHR. The institution of Dr. Marrie has received research support from MS Canada. The institution of Dr. Marrie has received research support from National MS Society. The institution of Dr. Marrie has received research support from Crohn's and Colitis Canada. The institution of Dr. Marrie has received research support from US Department of Defense. The institution of Dr. Marrie has received research support from The Arthritis Society. The institution of Dr. Marrie has received research support from CMSC.
Brenda L. Banwell, MD, FAAN (Childrens Hospital of Philadelphia) Dr. Banwell has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Banwell has received personal compensation in the range of $0-$499 for serving as a Consultant for UCB. Dr. Banwell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Banwell has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Banwell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Banwell has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Banwell has received research support from National MS Society. The institution of Dr. Banwell has received research support from NIH.
Amit Bar-Or, MD, FRCPC (University of Pennsylvania) Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merk/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for cabaletta. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. The institution of Dr. Bar-Or has received research support from Novartis. The institution of Dr. Bar-Or has received research support from Biogen. The institution of Dr. Bar-Or has received research support from Roche/Genentech.