S-4: Differentiation and function of follicular helper T cells (Tfh)

Abstract

T cell help to B cells is a fundamental aspect of adaptive immunity and the generation of B cell memory. The development of virtually all neutralizing antibodies is CD4 T cell dependent. Tfh cells are the unique and specialized T cells for B cell help, required for development of germinal centers, affinity matured Abs, and most B cell memory (memory B cells and memory plasma cells (PC)). T cell help is frequently a primary limiting factor for these processes. Therefore understanding and controlling Tfh cells is important for developing true rational vaccine development strategies (Crotty, ARI 2011). Tfh cells are also potentially extremely useful biomarkers in human vaccine clinical trials. Tfh depend on expression of the transcription factor Bcl6, and there are multiple steps required for follicular helper T cell differentiation, including roles of IL-6, IL-21, and ICOS. Importantly, additional factors required for Tfh differentiation remain poorly defined. Tfh function is mediated in part by cytokines IL-21 and IL-4, as well as the chemokine CXCL13.