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

Çebi M., Çakar A., Durmuş H., Akan O., Aysal F., Parman Y., ...Daha Fazla

European Journal of Immunology, 2024 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1002/eji.202451268
  • Dergi Adı: European Journal of Immunology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Veterinary Science Database
  • Anahtar Kelimeler: Low-dose IL-2, Myasthenia gravis, Tfh, Tph, Treg
  • İstanbul Üniversitesi Adresli: Evet

Özet

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.