Follicular Helper CD4 T Cells (TFH)

Abstract

T cell help to B cells is a fundamental aspect of adaptive immunity and the generation of immunological memory. Follicular helper CD4 T (T_FH) cells are the specialized providers of B cell help. T_FHcells depend on expression of the master regulator transcription factor Bcl6. Distinguishing features of T_FHcells are the expression of CXCR5, PD-1, SAP (SH2D1A), IL-21, and ICOS, among other molecules, and the absence of Blimp-1 (prdm1). T_FHcells are important for the formation of germinal centers. Once germinal centers are formed, T_FHcells are needed to maintain them and to regulate germinal center B cell differentiation into plasma cells and memory B cells. This review covers T_FHdifferentiation, T_FHfunctions, and human T_FHcells, discussing recent progress and areas of uncertainty or disagreement in the literature, and it debates the developmental relationship between T_FHcells and other CD4 T cell subsets (Th1, Th2, Th17, iTreg).