Increased Intrathecal Activity of Follicular Helper T Cells in Patients with Relapsing-Remitting Multiple Sclerosis

Friday, June 24, 2022

2:25 PM – 2:40 PM PT

Location: Salons 1/2

Authors: Rikke Holm Hansen, MSc (Presenting Author) - Danish multiple sclerosis center, Rigshospitalet; Jacob Talbot, MD (Co-Author) - Danish multiple sclerosis center, Rigshospitalet; Helene HÃ¸jsgaard Chow, MD, PhD (Co-Author) - Danish multiple sclerosis center, Rigshospitalet; Malene Bredahl Hansen, MSc, Phd (Co-Author) - Danish multiple sclerosis center, Rigshospitalet; Finn Sellebjerg, MD, PhD, DMSc (Co-Author) - Danish Multiple Sclerosis Center, Copenhagen University Hospital Rigshospitalet, and Department of Clinical Medicine, University of Copenhagen; Marina R. von Essen, MSc, Phd (Co-Author) - Danish Multiple Sclerosis Center, Rigshospitalet

Presenting Author(s)

RH

Rikke Holm Hansen, MSc

Cand. Scient, Phd stud.
Danish multiple sclerosis center, Rigshospitalet
København Ø, Hovedstaden, Denmark

Chair(s)

Terri Laufer, MD

Associate Professor of Medicine
University of Pennsylvania
Philadelphia, Pennsylvania, United States

Follicular helper T (Tfh) cells play a critical role in protective immunity helping B cells produce antibodies and are likely implicated in the pathogenesis of various autoimmune diseases. This study investigated a possible role of Tfh cells in the pathogenesis of multiple sclerosis (MS).

We investigated phenotype, prevalence, and function of Tfh cells in blood and cerebrospinal fluid (CSF) from controls and patients with relapsing-remitting MS (RRMS) and primary progressive MS (PPMS). Additionally, we assessed the migratory capacity of Tfh cells in patients with MS in an in vitro blood-brain-barrier coculture assay of primary human astrocytes and brain microvascular endothelial cells.

This study identified two phenotypical and functionally distinct Tfh cell populations; CD25^- (Tfh1-like) and CD25^int (Tfh17-like) Tfh cells. Whereas only minor differences in Tfh cells were found in blood between patients with MS and controls, we observed an enrichment of CD25^-Tfh cells intrathecally in patients with RRMS and PPMS and CD25^int Tfh cells in patients with RRMS, compared to controls. Frequencies of intrathecal CD25^-Tfh cells and CD25^-Tfh:Tfr cell ratio correlated positively with IgG-index in patients with RRMS. Despite enrichment of intrathecal Tfh cells in patients with MS, no difference in the migratory capacity of peripheral Tfh cells was observed when compared to controls.

Our study indicates substantial changes in intrathecal Tfh dynamics in MS, particularly in patients with RRMS suggesting that the intrathecal inflammatory environment of patients with RRMS enables increased recruitment of peripheral Tfh cells rather than Tfh cells having an increased CNS migratory capacity.