Session Information
Date: Sunday, October 21, 2018
Title: T Cell Biology and Targets in Autoimmune and Inflammatory Disease Poster
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose:
IgG4-related disease (IgG4-RD) is a novel disease entity characterized by the infiltration of IgG4-secreting plasmablasts (PBs) and the generation of germinal centers in various affected organs. Several CD4+ T cell subsets including follicular helper T cells (Tfh), Th2 cells and Th1 (cytotoxic) cells have thus far been shown to be involved in the pathogenesis of IgG4-RD. Given the classic tenet that Th1 and Th2 are mutually exclusive, the above findings seem apparently contradictory and the underlying mechanism of this disease remain largely enigmatic. Here, we have thoroughly investigated the role of each CD4+ T cell subsets in patients with IgG4-RD.
Methods:
Peripheral blood (PB) mononuclear cells were obtained from 21 patients with IgG4-RD and 10 healthy controls (HC). The phenotype of CD4+ T cells was analyzed by a flow cytometry. CD4+ T cells were categorized as Th1, Th2, Th17, Th1/17, Tfh1, Tfh2, Tfh17, and respective activated populations by expression of CXCR5, CXCR3, CCR6 and PD-1. The frequency of SLAMF7+ (cytotoxic CD4+) cells was also evaluated among CD4+ T cells subsets. The proportion of CD4+ T cell subsets relative to whole CD4+ T cells in patients with IgG4-RD was compared with that in HC. Moreover, the number of CD4+ T cell subsets was assessed for correlation with the titers of serum IgG4.
Results:
The patients with IgG4-RD enrolled in this study were aged 66 ± 11 years and their titers of serum IgG4 were 372 ± 336 mg/dl. The frequency of Th1, Tfh1, Tfh2, and respective activated populations in patients with IgG4-RD patients was significantly increased compared with that in HC. Positive correlations were noted between the number of activated Tfh2 cells and the titer of serum IgG4 (r=0.46, p=0.03), while no correlations were observed between the number of any other activated subsets and the titer of serum IgG4, suggesting a critical role of this subset in generating IgG4-producing PBs. Notably, SLAMF7+ cells were almost exclusively observed in activated subsets of Th1 and Tfh1 cells in patients with IgG4-RD. This trend was more noticeable in patients with IgG4-RD than in HC. Moreover, the expression levels of SLAMF7 in activated Tfh1 cells were much higher than that in non-activated Tfh1 cells in patients with IgG4-RD (13.99±5.59% vs 0.81±0.56%, p<0.0001). Intriguingly enough, positive correlations were noted between the number of SLAMF7+ activated Tfh1 cells and the titer of serum IgG4 (r=0.45, p=0.039), while no correlations were observed between that of SLAMF+ activated Th1 cells and serum IgG4(r=0.11, p=0.63).
Conclusion:
Together, these suggest that activated Tfh2 cells and SLAMF7+ activated Tfh1 cells were involved with the pathogenesis of IgG4-RD via generating IgG4-producing PBs, while Th1 cells, especially SLAMF7+ cells, contribute to another pathologic processes in this disease via antibody-independent mechanisms such as the production of cytokines and cytotoxic molecules. These results might reconcile the previous contradictory findings and expand our knowledge of this novel disease entity.
To cite this abstract in AMA style:
Higashioka K, Ayano M, Kimoto Y, Mitoma H, Akahoshi M, Arinobu Y, Akashi K, Horiuchi T, Niro H. Distinct Roles of Tfh2, SLAMF7+ Tfh1 Cells and Th1 Cells in the Pathogenesis of IgG4-RD [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/distinct-roles-of-tfh2-slamf7-tfh1-cells-and-th1-cells-in-the-pathogenesis-of-igg4-rd/. Accessed .« Back to 2018 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/distinct-roles-of-tfh2-slamf7-tfh1-cells-and-th1-cells-in-the-pathogenesis-of-igg4-rd/