Session Title: T Cell Biology and Targets in Autoimmune Disease Poster II
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: To study the expression and function of T follicular helper cells and its subsets in IgG4-related disease(IgG4-RD).
Methods: Flow cytometry was performed to analyze the expression of Tfh cells and its subsets in untreated IgG4-RD patients(n=46) and healthy controls(n=33). With RT-PCR technique, the mRNA levels of Bcl-6, Blimp-1 and IL-21 from IgG4-RD patients were tested. The immunohistochemeistry and immunofluorescence technique were used to assess the location of IL-21 and Tfh cells in the involved tissues of IgG4-RD patients, respectively. Furthermore, by cells co-culture in vitro, the abilities of cTfh and its subsets to help B cells proliferation, apoptosis, differentiation, and producing IgG4 in IgG4-RD were explored.
Results: The frequencies of (CD4+CXCR5+)T, (CD4+CXCR5+ICOS+)T, (CD4+CXCR5+PD-1+)T, PD-1 in (CD4+CXCR5+ICOS+)T and (CD4+CXCR5+ICOS+PD-1) T in IgG4-RD patients were significantly higher in the perphrial blood and involved tissues of IgG4-RD patients compared with healthy controls, and the expression of these cells in those involved tissues were significantly higher than blood. Especially, the percentages of PD-1 in (CD4+CXCR5+ICOS+) cTfh cells was positively correlated to the serum levels of IgG, IgG4, IgG4/IgG%, the number of organ involved, and (CD19+CD24-CD38hi) B cell subset, which has been proved producing higher IgG4 than other B cells. mRNA Bcl6 in CD4+ T cells of IgG4-RD showed no difference with healthy controls while the mRNA Blimp-1 did. mRNA IL-21 in PBMCs of IgG4-RD was also higher compared with healthy controls, and positively correlated with serum levels of IgG4, IgG, IgG4/IgG%. In the involved tissues of IgG4-RD, both of the Tfh cells and IL-21 showed highly expression, mainly distributed around glandular cells or ectopic GC. Importantly, compared to healthy controls, cTfh cells in IgG4-RD patients could more efficiently facilitate B cells proliferation but inhibit cell apoptosis, and enhanced naive B cells differentiate into S memory B cells and (CD19+CD24-CD38hi) B cells, which resulted in much more IgG4 secretion. Furthermore, it was mainly cTfh1 and cTfh2 were significantly higher in IgG4-RD patients compared with healthy controls, and it was mainly cTfh1 and cTfh17 enhanced the ability of B cells proliferation but inhibited apoptosis, while it was mainly cTfh2, as well as cTfh1 promote B cells differentiate into plasma B cells and producing much more IgG4 antibodies in IgG4-RD.
Conclusion: Tfh cells, especially the expression of PD-1 in (CD4+CXCR5+ICOS+) T, as well as IL-21 play vital roles in the pathgenesis of IgG4-RD. Compared to healthy control, Tfh cells from IgG4-RD patient could more efficiently facilitate B cells proliferation but inhibit cell apoptosis, and promote B cells differentiation into S memory B and (CD19+CD24-CD38hi)B cells, which result in strong immune response and more IgG4 secretion. And it was cTfh2, as well as cTfh1 mainly performing the function.
To cite this abstract in AMA style:Chen Y, Zhang W, Zhang P, Zhu Y, Yang H. Aberrant Expression and Function of Human Circulating T Follicular Helper Cells and Its Subsets in IgG4 Related Disease [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/aberrant-expression-and-function-of-human-circulating-t-follicular-helper-cells-and-its-subsets-in-igg4-related-disease/. Accessed April 19, 2019.
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