In:
Annals of Clinical and Translational Neurology, Wiley, Vol. 9, No. 7 ( 2022-07), p. 962-976
Abstract:
Multiple sclerosis (MS) is a neuroinflammatory disease where immune cells cross the blood–brain barrier (BBB) into the central nervous system (CNS). What predisposes these immune cells to cross the BBB is still unknown. Here, we examine the possibility that genomic rearrangements could predisposespecific immune cells in the peripheral blood to cross the BBB and form sub‐populations of cells involved in the inflammatory process in the CNS. Methods We compared copy number variations in paired peripheral blood mononuclear cells (PBMCs) and cerebrospinal fluid (CSF) cells from MS patients. Thereafter, using next generation sequencing, we studied the T‐cell receptor beta (TRB) locus rearrangements and profiled the αβ T cell repertoire in peripheral CD4 + and CD8 + T cells and in the CSF. Results We identified deletions in the T‐cell receptor alpha/delta (TRA/D), gamma (TRG), and TRB loci in CSF cells compared to PBMCs. Further characterization revealed diversity of the TRB locus which was used to describe the character and clonal expansion of T cells in the CNS. T‐cell repertoire profiling from either side of the BBB concluded that the most frequent clones in the CSF samples are unique to an individual. Furthermore, we observed a difference in the proportion of expanded T‐cell clones when comparing samples from MS patients in relapse and remission with opposite trends in CSF and peripheral blood. Interpretation This study provides a characterization of the T cells in the CSF and might indicate a role of expanded clones in MS pathogenicity.
Type of Medium:
Online Resource
ISSN:
2328-9503
,
2328-9503
Language:
English
Publisher:
Wiley
Publication Date:
2022
detail.hit.zdb_id:
2740696-9
