The Ratio of Blood T Follicular Regulatory Cells to T Follicular Helper Cells Marks Ectopic Lymphoid Structure Formation While Activated Follicular Helper T Cells Indicate Disease Activity in Primary Sjögren's Syndrome

Abstract

The blood Tfr cell:Tfh cell ratio and PD-1+ICOS+ Tfh cells constitute potential novel biomarkers for different features of primary SS. While the blood Tfr cell:Tfh cell ratio is associated with ectopic lymphoid neogenesis, activated Tfh cells indicate disease activity.

FoxP3+CXCR5+CD4+ T cell frequencies are increased in peripheral blood of patients with primary Sjögren’s syndrome

“…a). Hence, we confirm the studies by Fonseca et al , demonstrating that the ratio between Tfr and Tfh is increased in SS patients.…”

“…However, we did not find a decrease in the total frequency of CXCR5 + CD4 + T cells in peripheral blood of SS patients, which was also confirmed by Fonseca et al. . Notably, however, a subgroup of SS patients presented an increase in CXCR5 + programmed death 1 (PD‐1) + CD4 + T cells, findings corroborated by Fonseca et al .…”

“…Notably, however, a subgroup of SS patients presented an increase in CXCR5 + programmed death 1 (PD‐1) + CD4 + T cells, findings corroborated by Fonseca et al . and Verstappen et al . .…”

Control of Germinal Center Responses by T-Follicular Regulatory Cells

“…The total number of cTfr in blood increases after vaccination, while the proportion of them that are CD45RA + drops (68, 69). cTfr are also increased as a proportion of Tregs in patients with ongoing Sjögren's syndrome (SS), and the Tfr/Tfh ratio strongly correlates with both autoantibody production and activated (PD-1 + ICOS + ) T-cell infiltration into the minor salivary glands of patients (68, 75). In the context of infection, cTfr expand during chronic viral and parasitic infections such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and Schistosoma japonica (76–78) The increase of cTfr cell frequency in patients chronically infected with either HBV or HCV showed strong correlation with serum viral load in both infections.…”

Contribution of FoxP3+ Tfr cells to overall human blood CXCR5+ T cells

“…may provide an explanation for salivary gland infiltration by CXCR5‐expressing cells . We also observed a substantial number of CXCR5‐expressing cells within salivary glands of SS patients, many of those also expressing FoxP3 . However, whether increased serum levels of CXCL13 in SS patients are due exclusively to secretion from salivary gland infiltrating cells remains an open question.…”