Low-dose IL-2 fails to expand Tregs after alemtuzumab: insight into impaired immune tolerance in multiple sclerosis

Clicks: 17
ID: 313791
2026
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Steady

Ranked #373 of 457 articles by views in Brain research

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 457 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Regulatory T cells (Tregs) are essential for preventing autoimmunity. They depend upon interleukin-2 (IL-2) for optimal function and due to high expression of the CD25 subunit of the IL-2 receptor, are 10-fold more sensitive to IL-2 than effector T cells (Teffs). Consequently low-dose IL-2 can be used to preferentially expand Tregs, a therapeutic strategy which has shown promise in a number of autoimmune and inflammatory conditions - including graft-versus-host disease and lupus, where IL-2 driven expansion correlates with improvements in some clinical markers of disease activity. Autoimmunity is a frequent delayed complication of treatment with the lymphocyte-depleting drug alemtuzumab in relapsing-remitting multiple sclerosis (RRMS). Here, using in vitro assays, a pre-clinical mouse model, and an experimental medicine study, we investigated whether low-dose IL-2 could selectively expand Tregs in alemtuzumab-treated RRMS patients. Six months after alemtuzumab treatment, the frequency of patient-derived naïve CD4+ Teffs expressing high-affinity IL-2 receptors increased from 30.11+/-5.09% to 72.88 +/-5.57%, and the density of receptors per cell increased, rendering them six times more sensitive to IL-2 in vitro, at concentrations that typically favour Tregs. Using a human CD52-expressing transgenic mouse model of alemtuzumab treatment, we found that IL-2 was still able to preferentially expand Tregs, but only when administered at a later time point, corresponding to more than 6 months post-treatment in patients. Guided by these findings, we evaluated low-dose IL-2 for Treg expansion in a prospective open-label mechanistic study of RRMS patients who had received alemtuzumab more than 6 months previously. IL-2, at a dose and frequency similar to that previously shown to expand Tregs in autoimmune diabetes (0.3 x 106 IU/m2 twice a week), was well tolerated and safe, but unexpectedly failed to expand Tregs. We discuss the potential reasons underlying this lack of response, ruling out sIL2RA-related neutralisation, and instead considering ceiling effects on Treg proliferation, Treg exhaustion and intrinsic Treg dysfunction in MS as possible contributors. Together, our findings demonstrate that low-dose IL-2 alone is not an effective strategy for promoting Treg expansion post-alemtuzumab, and is therefore not a viable approach by itself for preventing post-treatment autoimmune complications.
Reference Key
openalex_W7160991655 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Zoya Georgieva, Sarah Howlett, Daniel B. Rainbow, Valerie Coppard, Lou Ellis, Lorna B. Jarvis, E Williams, Jennie H M Yang, Bo Sun, Timothy Tree, A Coles, Linda S Wicker, Joanne Jones
Are you one of these authors? Claim your profile
Journal Brain research
Year 2026
DOI
10.1093/brain/awag171
URL
https://doi.org/10.1093/brain/awag171
Keywords Keywords not found

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.