Insights Into the Molecular Mechanisms of T Follicular Helper-Mediated Immunity and Pathology

Abstract

T follicular helper (Tfh) cells play key role in providing help to B cells during germinal center (GC) reactions. Generation of protective antibodies against various infections is an important aspect of Tfh-mediated immune responses and the dysregulation of Tfh cell responses has been implicated in various autoimmune disorders, inflammation, and malignancy. Thus, their differentiation and maintenance must be closely regulated to ensure appropriate help to B cells. The generation and function of Tfh cells is regulated by multiple checkpoints including their early priming stage in T zones and throughout the effector stage of differentiation in GCs. Signaling pathways activated downstream of cytokine and costimulatory receptors as well as consequent activation of subset-specific transcriptional factors are essential steps for Tfh cell generation. Thus, understanding the mechanisms underlying Tfh cell-mediated immunity and pathology will bring into spotlight potential targets for novel therapies. In this review, we discuss the recent findings related to the molecular mechanisms of Tfh cell differentiation and their role in normal immune responses and antibody-mediated diseases.

PDL1 blockage increases fetal resorption and Tfr cells but does not affect Tfh/Tfr ratio and B-cell maturation during allogeneic pregnancy

“…Tfh cells are essential for GC formation and maintenance, and provide survival signals for high affinity B cells within the GC for their differentiation to isotypeswitched antibody secreting cells and memory B cells 38,39 . Although the function of Tfr cells in the GC has not been completely clarified, the mainstream view currently is that Tfr cells restrict Tfh-and B-cell proliferation and exert an inhibitory action on antibody production [40][41][42] .…”

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

“…Accumulated studies have shown that follicular helper T cells (TFH) play an important role in assisting the immune function of human B cells. TFH is differentiated and developed from the initial CD4 + T cells in the germinal center (GC), and secretes IL-21 to promote self-proliferation and differentiation (9). TFH cells exist in the germinal center and peripheral blood, and circulating TFH can be divided into TFH1, TFH2, and TFH17 subsets, according to the expression of CXCR3 and CCR6 (10).…”

The Immunotherapeutic Effect of SIRPα-Silenced DCs against Cervical Cancer

“…a Significant differences compared with that of the DC control, p < 0:001; b no significant differences compared with that of the LPS control, p > 0:05; c significant differences compared with that of the LPS control or Ad-shControl, p < 0:05. T cell-mediated immunity and pathology will also bring into many spotlight potential targets for novel cancer therapies [33]. In order to activate the full immunostimulatory talent of DCs, SIRPα which initiated a negative signal pathway to regulate the maturation of DCs was knocked down in this research.…”