Follicular Helper CD4 T Cells (TFH)

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