TY - JOUR
T1 - Early adaptive immune activation detected in monozygotic twins with prodromal multiple sclerosis
AU - Beltrán, Eduardo
AU - Gerdes, Lisa Ann
AU - Hansen, Julia
AU - Flierl-Hecht, Andrea
AU - Krebs, Stefan
AU - Blum, Helmut
AU - Ertl-Wagner, Birgit
AU - Barkhof, Frederik
AU - Kümpfel, Tania
AU - Hohlfeld, Reinhard
AU - Dornmair, Klaus
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Multiple sclerosis (MS) is a disabling disease of the CNS. Inflammatory features of MS include lymphocyte accumulations in the CNS and cerebrospinal fluid (CSF). The preclinical events leading to established MS are still enigmatic. Here we compared gene expression patterns of CSF cells from MS-discordant monozygotic twin pairs. Six "healthy" co-twins, who carry a maximal familial risk for developing MS, showed subclinical neuroinflammation (SCNI) with small MRI lesions. Four of these subjects had oligoclonal bands (OCBs). By single-cell RNA sequencing of 2752 CSF cells, we identified clonally expanded CD8+ T cells, plasmablasts, and, to a lesser extent, CD4+ T cells not only from MS patients but also from subjects with SCNI. In contrast to nonexpanded T cells, clonally expanded T cells showed characteristics of activated tissue-resident memory T (TRM) cells. The TRM-like phenotype was detectable already in cells from SCNI subjects but more pronounced in cells from patients with definite MS. Expanded plasmablast clones were detected only in MS and SCNI subjects with OCBs. Our data provide evidence for very early concomitant activation of 3 components of the adaptive immune system in MS, with a notable contribution of clonally expanded TRM-like CD8+ cells.
AB - Multiple sclerosis (MS) is a disabling disease of the CNS. Inflammatory features of MS include lymphocyte accumulations in the CNS and cerebrospinal fluid (CSF). The preclinical events leading to established MS are still enigmatic. Here we compared gene expression patterns of CSF cells from MS-discordant monozygotic twin pairs. Six "healthy" co-twins, who carry a maximal familial risk for developing MS, showed subclinical neuroinflammation (SCNI) with small MRI lesions. Four of these subjects had oligoclonal bands (OCBs). By single-cell RNA sequencing of 2752 CSF cells, we identified clonally expanded CD8+ T cells, plasmablasts, and, to a lesser extent, CD4+ T cells not only from MS patients but also from subjects with SCNI. In contrast to nonexpanded T cells, clonally expanded T cells showed characteristics of activated tissue-resident memory T (TRM) cells. The TRM-like phenotype was detectable already in cells from SCNI subjects but more pronounced in cells from patients with definite MS. Expanded plasmablast clones were detected only in MS and SCNI subjects with OCBs. Our data provide evidence for very early concomitant activation of 3 components of the adaptive immune system in MS, with a notable contribution of clonally expanded TRM-like CD8+ cells.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85074379447&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31566584
U2 - https://doi.org/10.1172/JCI128475
DO - https://doi.org/10.1172/JCI128475
M3 - Article
C2 - 31566584
SN - 0021-9738
VL - 129
SP - 4758
EP - 4768
JO - Journal of clinical investigation
JF - Journal of clinical investigation
IS - 11
ER -