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.