# Myelin-specific IL2 + T-cells are associated with last occurring relapse severity in relapsing–remitting multiple sclerosis

## TL;DR

This study finds that specific T-cells producing IL2 in response to myelin proteins are linked to the severity of the most recent relapse in multiple sclerosis patients.

## Contribution

The study identifies a novel association between IL2-producing central memory T-cells and recent relapse severity in relapsing–remitting multiple sclerosis.

## Key findings

- Higher IL2 responses to PLP correlate with the severity of the last relapse in RRMS patients.
- Increased central memory T-cells were observed in RRMS patients compared to healthy subjects.
- IL2 responses to PLP were more frequent and stronger in RRMS patients than in healthy controls.

## Abstract

Autoreactive T-cells against myelin are implicated in multiple sclerosis (MS) however, the functional relevance of IL2-producing central memory T-cells and IFNɣ-producing effector T-cells have not been assessed. In this study we aimed to t investigate association of IL2 + and IFNγ + myelin reactive memory T-cells with MS severity and progression. Thirty relapsing–remitting MS (RRMS) patients and 32 age-matched healthy subjects (HS) were analyzed. Peripheral Blood Mononuclear Cells (PBMC) responses to proteolipid protein (PLP), myelin basic protein (MBP), and myelin oligodendrocyte glycoprotein (MOG) were assessed using IFNγ/IL2-FluoroSpot assay and correlated with disease severity and progression. Flow cytometry was performed to characterize central (CD45RO+CD62L+) and effector memory (CD45RO+CD62L-) T-cell subsets. Patients showed increased frequency and magnitude of IL2 responses to PLP compared with HS. Higher PLP-induced IL2 responses were in correlation with clinical severity of the last occurring relapse, including EDSS, EDSS change, and longer time from last occurring relapse (p < 0.05). Odds ratios (OR) confirmed associations between IL2-responses and last occurring relapse severity (OR range 5.3–22.5). Flow cytometry confirmed increase of central memory CD4 + and CD8 + T-cells in RRMS, whereas effector memory frequencies were unchanged. In RRMS, circulating PLP-reactive IL2 + central memory T-cells are linked to severity of last occurring relapse, representing an immunological imprint of recent disease activity rather than cumulative burden.

The online version contains supplementary material available at 10.1038/s41598-026-39859-9.