Low-dose IL-2 therapy limits the reduction in absolute numbers of circulating regulatory T cells in rheumatoid arthritis

Sheng-Xiao Zhang; Jia Wang; Cai-Hong Wang; Rui-Huan Jia; Ming Yan; Fang-Yuan Hu; Guang-Ying Liu; Xue-Yu Liu; Jing Luo; Chong Gao; Xiao-Feng Li

doi:10.1177/1759720X211011370

Low-dose IL-2 therapy limits the reduction in absolute numbers of circulating regulatory T cells in rheumatoid arthritis

Ther Adv Musculoskelet Dis. 2021 Apr 28:13:1759720X211011370. doi: 10.1177/1759720X211011370. eCollection 2021.

Authors

Affiliations

¹ Department of Rheumatology, the Second Hospital of Shanxi Medical University.
² Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
³ College of Data Science, Taiyuan University of Technology, Taiyuan, Shanxi, China.
⁴ Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

Background: Circulating regulatory T cells (Tregs) are responsible for mediating immune tolerance and maintaining immunological homeostasis. Decreases in Tregs may be involved in the onset of rheumatoid arthritis (RA). Low-dose interleukin-2 (IL-2) has been considered for the treatment of inflammatory diseases mediated by T cells. This study focused on the status of circulating CD4⁺T subsets and the clinical feasibility of IL-2 therapies in patients with RA.

Methods: The subjects included 888 patients with RA and 100 healthy controls (HCs); 233 RA patients received IL-2 treatment with 0.5 million international units (MIU)/day from days 1 through 5. The demographic features, disease activity, and levels of CD4+T cells measured by modified flow cytometry were collected in all RA patients before and after treatment.

Results: RA patients had lower absolute Treg counts (but not Th17) compared with HCs, which was associated with disease activity; previously treated RA patients had the fewest circulating Tregs (p < 0.05). Patients treated with low-dose IL-2 had a three-fold increase in absolute anti-inflammatory Treg counts, as well as a two-fold increase in the other CD4⁺T subsets. Moreover, post-treatment levels of markers of disease activity in RA patients treated with IL-2 were significantly lower than the baseline values (p < 0.001), with no apparent side effects.

Conclusion: Decreased absolute counts of circulating CD4⁺T lymphocyte subsets were observed in patients with RA. Circulating Tregs, which mediate immune tolerance, may be involved in the pathogenesis and progression of RA; however, this was ameliorated by low-dose IL-2, without obvious side effects.

Plain language summary: Low-dose IL-2 treatment for rheumatoid arthritis • Circulating Tregs may be involved in the pathogenesis and progression of RA.• The absolute count of Tregs was significantly correlated with disease activity measures.• Low-dose IL-2 was able to effectively expade Tregs and help for RA patients' symptoms remission without evaluated side effects.

Keywords: immunoregulation; low-dose IL-2; regulatory T cells; rheumatoid arthritis.