Follicular helper T cells, or ThF cells, are antigen-experienced CD4+ T cells found in the lymph node and are identified as being PSGL-1- and CXCR5+. ThF cells are found at the periphery of B cell follicles and appear to mediate naïve B cell activation and germinal center formation, probably through the expression of ligand for CD40 and the secretion of Th1– and Th2-like cytokines. It is possible that ThF 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.

Inducible T-cell co-stimulator (CD278 or ICOS) has proven to be a particularly critical signal for ThF cells, although it is not clear if that role is in induction or progressive maturation. Also Bcl-6 is a factor identified in ThF cells, but it may have roles that extend beyond this subset, because it has been implicated in memory CD8+ T cell development.

Finally, it has been shown that dysregulated ThF cells can cause systemic autoimmunity and auto-antibody production or contribute to T cell–mediated organ-specific autoimmunity.


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