Aberrant Expansion and Function of Follicular Helper T Cell Subsets in IgG4-Related Disease

Arthritis & Rheumatology
Yu ChenPeter E Lipsky

Abstract

To determine the number and function of follicular helper T (Tfh) cell subsets in IgG4-related disease (IgG4-RD). Mononuclear cells from the peripheral blood and involved tissue of patients with IgG4-RD were assessed for Tfh cells and their subsets, and levels of B cell lymphoma 6 (Bcl-6), B lymphocyte-induced maturation protein 1 (BLIMP-1), and interleukin-21 (IL-21) messenger RNA (mRNA). Immunohistochemical and immunofluorescence techniques were used to assess the involved tissue of patients to determine the location of IL-21, Bcl-6, and CD4+CXCR5+ Tfh cells. Furthermore, the ability of circulating Tfh (cTfh) cell subsets to induce B cell proliferation, apoptosis, and differentiation and to produce IgG4 was explored in cell cocultures in vitro. Frequencies of cTfh cells were significantly increased in the peripheral blood of patients with IgG4-RD, and even higher frequencies were observed in the involved tissue. Percentages of programmed cell death protein 1 in CD4+CXCR5+ICOS+ cTfh cells were positively correlated with the serum levels of IgG and IgG4, IgG4:IgG ratio, number of involved organs, and frequency of CD19+CD24-CD38high plasmablasts/plasma cells. Levels of BLIMP-1 and IL-21 mRNA in peripheral CD4+ T cells were incre...Continue Reading

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Citations

Apr 30, 2020·Rheumatology·Federica MaritatiAugusto Vaglio
Sep 18, 2020·Nature Reviews. Rheumatology·Cory A Perugino, John H Stone
Sep 14, 2019·Clinical and Translational Gastroenterology·Mitsuhiro AkiyamaTsutomu Takeuchi
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Methods Mentioned

BETA
flow cytometry
ELISA

Software Mentioned

SPSS
FlowJo
Tree Star
ZEN Lite microscope

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