In vitro modulation of T cells in myasthenia gravis by low-dose IL-2

Abstract

Follicular helper (Tfh), peripheral helper (Tph), and regulatory (Treg) T cells are involved in myasthenia gravis (MG) pathogenesis, an autoimmune disorder arising from autoantibodies targeting neuromuscular junction proteins. This study explores the impact of low-dose IL-2 on Tfh, Tph, and Treg cells in vitro in MG. Acetylcholine-receptor antibody-positive MG (AChR-MG), muscle-specific kinase antibody-positive MG (MuSK-MG) patients, and healthy controls (HC) were studied. Blood cells were cultured with/without IL-2 and compared by the ratios of IL-2 stimulated/unstimulated cultures. In both AChR-MG and MuSK-MG patients, CD25⁺FoxP3⁺Tregs were lower, while CXCR5⁺PD-1⁺ or ICOS⁺Tfh and CXCR5^-PD-1⁺ or ICOS⁺Tph cells were higher compared with HC. Among the MG group, the FoxP3⁺ Treg cells in AChR-MG patients were even lower compared with MuSK-MG patients. In vitro IL-2 stimulation increased Tregs in all groups while decreasing PD-1⁺/ICOS⁺Tfh and PD-1⁺/ICOS⁺Tph populations. The fold-increase ratio of Tregs and the fold-decrease ratio of PD-1⁺ or ICOS⁺Tfh and ICOS⁺Tph cells in AChR-MG and MuSK-MG patients were greater than in HCs. Low-dose IL-2 treatment may balance Tfh, Tph, and Treg cells in MG patients, offering a potential opportunity for disease modulation.

Keywords: Low‐dose IL‐2; Myasthenia gravis; Tfh; Tph; Treg.