Follicular B helper T cells
Follicular helper T cells (also known as T follicular helper cells and abbreviated as TFH), are
It is possible that TFH cells might arise as branches in the Th1 and Th2 differentiation pathways but their precise lineage relationship to the other effector CD4+ T cell subsets is still uncertain. Studies have however shown that TFH have distinct gene expression profiles, supporting the theory that TFH are a subset of CD4+ T cells distinct from
Biomolecular characterization
The inducible T-cell co-stimulator (CD278 or ICOS) is proven to provide a particularly critical signal for TFH cells since experimental mice deficient in ICOS are unable to develop any TFH.[7] Additionally, it has been shown that ICOS induces the secretion of IL-21 cytokine by activated CD4+ T cells and that IL-21 plays a crucial role in the development of TFH cells and germinal centers.[8][9] Also Bcl-6 is a transcription factor identified in TFH cells, but it may have roles that extend beyond this subset, because it has also been implicated in memory CD8+ T cell development.[10]
In germinal centers, antigen-experienced TFH cells rapidly upregulate the expression of CD40L, which binds and stimulates the B cell surface receptor CD40.
Classes of TFH cells
TFH cells formed early in the nascent stages of a germinal center reaction are formally called pre-TFH cells. They are uniquely found predominantly at the border of the T cell zone that merges with the B cell follicles and germinal centers. Pre-TFH cells are functionally very similar to other TFH cells in facilitating germinal center B cell reactions; however, they are also capable of driving follicular B cell development adjacent to and outside of germinal centers to produce quickly responsive but non-durable plasma cell-driven antibody responses (known as the extrafollicular response).
Those TFH cells specifically residing within a mature germinal center are sometimes referred to as GC TFH cells (for germinal center TFH cells) to distinguish them from pre-TFH cells.
While TFH cells are found primarily in the secondary lymphoid organs, a small proportion circulate in the blood and are termed "peripheral" T follicular helper cells (pTFH). These cells can be identified by their expression of IL-21 upon stimulation.[16]
Medical relevance
Generating lasting immune memory
TFH cells are considered an indispensable T cell subset in the generation and maintenance of
With normal aging comes a gradual diminishing of the body's immune system. This phenomenon called
Avoiding autoimmunity
Unchecked or overactive TFH cell immune responses have the potential to mount unwarranted germinal centers, composed of aberrantly mutated
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