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Review
. 2019 May 21;50(5):1132-1148.
doi: 10.1016/j.immuni.2019.04.011.

T Follicular Helper Cell Biology: A Decade of Discovery and Diseases

Shane Crotty  1
Affiliations
Review

T Follicular Helper Cell Biology: A Decade of Discovery and Diseases

Shane Crotty. Immunity. .

Abstract

Helping B cells and antibody responses is a major function of CD4+ T cells. It has been 10 years since the publication of Bcl6 as the lineage-defining transcription factor for T follicular helper (Tfh) differentiation and the requirement of Tfh cells as the specialized subset of CD4+ T cells needed for germinal centers (the microanatomical sites of B cell mutation and antibody affinity maturation) and related B cell responses. A great deal has been learned about Tfh cells in the past 10 years, particularly regarding their roles in a surprising range of diseases. Advances in the understanding of Tfh cell differentiation and function are discussed, as are the understanding of Tfh cells in infectious diseases, vaccines, autoimmune diseases, allergies, atherosclerosis, organ transplants, and cancer. This includes discussion of Tfh cells in the human immune system. Based on the discoveries to date, the next decade of Tfh research surely holds many more surprises. VIDEO ABSTRACT.

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Figures

Figure 1.
Figure 1.. Features of Tfh cells.
Tfh cell differentiation is induced by DCs in the presence of antigen and signals from the microenvironment. Tfh cell versus non-Tfh cell differentiation bifurcates early, based on the balance of inductive and inhibitory signals. Some intermediate cell fates are also possible (grey). Early Tfh cells then subsequently differentiate to GC-Tfh cells.
Figure 2.
Figure 2.. Signals to and from Tfh cells.
Tfh cells receive signals from a number of cell types that can regulate Tfh differentiation and/or function. Tfh cells function by providing help to B cells at a series of stages of antigen-specific B cell differentiation. BAct, activated B cells. BGC, GC B cells. BPC, PC. Bpb, plasmablasts. BMem, memory B cells.
Figure 3.
Figure 3.. Tfh and B cell response kinetics and interactions.
A. A time series of Tfh differentiation and function. Details of the steps are summarized in the main text. For simplicity, only one TF is indicated in each cell. TCF1 expression is retained in Tfh cells and not non-Tfh effector cells. An animated versions is included. B. Tfh functions and signals that regulate BGC cycling, BGC➔BPC differentiation, and BGC➔BMem differentiation. “Int” = intermediate.
Figure 4.
Figure 4.. Relationships of Tfh cells to diseases.
Over the past decade Tfh cells have been associated with a wide range of diseases, with the Tfh cells contributing protective or pathogenic roles in different contexts, discussed in the main text.
See this image and copyright information in PMC

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