The immune imbalance between follicular regulatory and helper T cells in myelin oligodendrocyte glycoprotein IgG-associated disease

• DOI: 10.1016/j.clim.2023.109734
• Publication Date: 2023-08-11T01:41:29Z
• Authors: Xuechun Chang; Kexin Jiao; Danjie Wang; Yufan Zhou; Zhao Zhao; Ying Xing; Jingzi Zhangbao; Chuanzhen Lu; Jun Wang; Chao Quan
• Keywords: Interleukin 1 Receptor Antagonist Protein; B-Lymphocytes; Immunoglobulin G; Humans; Myelin-Oligodendrocyte Glycoprotein; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; 3. Good health

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a newly defined inflammatory demyelinating disease of the central nervous system. Currently, no immuno-modulatory treatment has been approved for MOGAD. We explored the function of follicular regularoty T (Tfr) and follicular helper T (Tfh) cells in patients with MOGAD. The number of circulating Tfr and Tfh cells and their expression of functional markers were accessed by flow cytometry. Circulating Tfr, Tfh, and B cells were further sorted and co-cultured in vitro to examine the influence of Tfr on Tfh-mediated B cell differentiation. In patients with MOGAD, the percentage of circulating PD-1hi Tfh cells elevated while the frequency of circulating activated Tfr cells decreased significantly. The Tfh/Tfr ratios positively correlated with the percentage of plasmblasts. In vitro, Tfh cells from patients with MOGAD exhibited a stronger capacity to promote the differentiation of plasmablasts through producing interleukin (IL)-21 than non-Tfh cells from patients, whereas Tfr cells suppressed this Tfh-mediated plasmablasts expansion, to a similar extent of IL-1 receptor antagonist (IL-1Ra). In conclusion, we revealed an immune imbalance of Tfr and Tfh cells in MOGAD. Tfr and IL-1Ra could be potential therapeutic targets in MOGAD.