Perivascular tissue resident memory T cells as therapeutic target in multiple sclerosis

TY - JOUR

T1 - Perivascular tissue resident memory T cells as therapeutic target in multiple sclerosis

AU - Smolders, Joost

AU - Fransen, Nina L

AU - Hsiao, Chen-Chih

AU - Hamann, Jörg

AU - Huitinga, Inge

PY - 2020

Y1 - 2020

N2 - INTRODUCTION: Multiple sclerosis (MS) is characterized by inflammatory attacks of infiltrating leukocytes at onset but evolves into a smoldering, progressive disease within the central nervous system at its later stages. The authors discuss the contribution of white matter lesions to the pathology of advanced MS, thereby paying particular attention to the role of T cells.AREAS COVERED: Diagnostic biopsy and autopsy studies of white matter lesions in early MS show different pathological patterns of demyelination and leukocyte infiltration. Brain autopsies from advanced MS display substantial inflammation without distinct patterns and suggest a role for perivascular CD8+ tissue-resident memory T (TRM) cells in active and mixed active/inactive MS white matter lesions. When compared to control and normal-appearing white matter, these lesions are enriched for parenchymal CD8+ T cells. In the perivascular space, cuffs containing CD8+ TRM cells are observed also in progressive MS, and could be sites of local reactivation.EXPERT OPINION: Recent findings point towards the perivascular space as an immunological hotspot, which could be targeted in order to suppress a contribution of TRM cells to ongoing white matter lesion activity in advanced progressive MS. The authors discuss approaches, which may be explored to suppress TRM-cell reactivation in the perivascular space.

AB - INTRODUCTION: Multiple sclerosis (MS) is characterized by inflammatory attacks of infiltrating leukocytes at onset but evolves into a smoldering, progressive disease within the central nervous system at its later stages. The authors discuss the contribution of white matter lesions to the pathology of advanced MS, thereby paying particular attention to the role of T cells.AREAS COVERED: Diagnostic biopsy and autopsy studies of white matter lesions in early MS show different pathological patterns of demyelination and leukocyte infiltration. Brain autopsies from advanced MS display substantial inflammation without distinct patterns and suggest a role for perivascular CD8+ tissue-resident memory T (TRM) cells in active and mixed active/inactive MS white matter lesions. When compared to control and normal-appearing white matter, these lesions are enriched for parenchymal CD8+ T cells. In the perivascular space, cuffs containing CD8+ TRM cells are observed also in progressive MS, and could be sites of local reactivation.EXPERT OPINION: Recent findings point towards the perivascular space as an immunological hotspot, which could be targeted in order to suppress a contribution of TRM cells to ongoing white matter lesion activity in advanced progressive MS. The authors discuss approaches, which may be explored to suppress TRM-cell reactivation in the perivascular space.

U2 - 10.1080/14737175.2020.1776609

DO - 10.1080/14737175.2020.1776609

M3 - Article

C2 - 32476499

SN - 1473-7175

VL - 20

SP - 835

EP - 848

JO - Expert Review of Neurotherapeutics

JF - Expert Review of Neurotherapeutics

ER -