Follicular helper T cell in immunity and autoimmunity

Abstract

The traditional concept that effector T helper (Th) responses are mediated by Th1/Th2 cell subtypes has been broadened by the recent demonstration of two new effector T helper cells, the IL-17 producing cells (Th17) and the follicular helper T cells (Tfh). These new subsets have many features in common, such as the ability to produce IL-21 and to express the IL-23 receptor (IL23R), the inducible co-stimulatory molecule ICOS, and the transcription factor c-Maf, all of them essential for expansion and establishment of the final pool of both subsets. Tfh cells differ from Th17 by their ability to home to B cell areas in secondary lymphoid tissue through interactions mediated by the chemokine receptor CXCR5 and its ligand CXCL13. These CXCR5+ CD4+ T cells are considered an effector T cell type specialized in B cell help, with a transcriptional profile distinct from Th1 and Th2 cells. The role of Tfh cells and its primary product, IL-21, on B-cell activation and differentiation is essential for humoral immunity against infectious agents. However, when deregulated, Tfh cells could represent an important mechanism contributing to exacerbated humoral response and autoantibody production in autoimmune diseases. This review highlights the importance of Tfh cells by focusing on their biology and differentiation processes in the context of normal immune response to infectious microorganisms and their role in the pathogenesis of autoimmune diseases.

The Imbalance of Circulating Follicular Helper T Cells and Follicular Regulatory T Cells Is Associated With Disease Activity in Patients With Ulcerative Colitis

“…The main function of TFH is to initiate and regulate germinal center reaction and germinal center B cell maturation and differentiation (11). GC abnormal reaction occurs when the number or function of TFH cells is changed, resulting in the production of a large number of plasma cells and memory B cells, and more high-affinity antibodies and inflammatory factors (11)(12)(13). TFH is significantly increased in peripheral blood of systemic lupus erythematosus (SLE) patients and is positively correlated with autoantibody titer and disease activity (14).…”

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

“…Abnormal expression and/or dysfunction of Tfh cells can be involved in the development of autoimmune disease, with the resultant production of increased concentrations of autoantibodies . IgG4‐related disease (IgG4‐RD) is a newly recognized immune‐mediated fibroinflammatory disease that is characterized by enlargement of tissues or organs, abundant IgG4+ plasma cell infiltration in damaged organs, and elevated serum IgG4 levels .…”

Activated inducible co-stimulator-positive programmed cell death 1-positive follicular helper T cells indicate disease activity and severity in ulcerative colitis patients

“…Tfh cells are crucial for the differentiation and development of B cells, and abnormality of effective B cells was confirmed to be involved in the pathogenesis of UC [9][10][11][12][13]. To further study the clinical significance of circulating ICOS + , PD-1 + and ICOS + PD-1 + Tfh cells in the pathogenesis of UC, we analyzed their associations with functional B cell subsets.…”

“…As is well known, the normal maintenance of B cell differentiation and function requires the coordinated regulation of follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells [10][11][12]. Tfh cells provide important signals to regulate B cells to differentiate into effective B cells and secrete high-affinity and isotype-switched antibodies [10,12,13].…”