Follicular Helper CD4 T Cells (T_FH)

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(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).

Expansion of Tfh‐like cells during chronic Salmonella exposure mediates the generation of autoimmune hypergammaglobulinemia in MyD88‐deficient mice

“…Tfh cells are a subset of activated CD4 1 T cells and are specialized to regulate B-cell-mediated humoral immunity [11,27]. Furthermore, a recent study suggested that persistent infection of virus could drive the differentiation of helper T cells to Tfh cells [28].…”

“…Tfh cells express ICOS, CD40L, PD-1, and CXCR5 on the cell surface, but their function has not been fully elucidated. ICOS-ICOSL interaction, IL-21 and IL-6, but not IL-4, IFN-g, and TGF-b, are important for the generation of Tfh cells, suggesting that Tfh cells are a distinct subset of CD4 1 helper T cells, independent of Th1, Th2, and Th17 cells [9][10][11]. Further, PD-1 expressed on Tfh was recently found to be important for the survival and selection of B cells in the GC [12].…”

The darker side of follicular helper T cells: from autoimmunity to immunodeficiency

“…12 These markers contribute to the migration of T FH cells and the interaction of T FH cells with B cells to promote Bcell responses against pathogens. The binding of CXCR5 on T FH cells with its cognate ligand, CXCL-13, in GC facilitates the migration of T FH cells to B-cell follicles for their interaction with B cells.…”

T cell epitope engineering: an avian H7N9 influenza vaccine strategy for pandemic preparedness and response

“…Generation of antibody after vaccination depends on follicular helper T cells (Tfh), a subset of CD4 + T cells that are specialized for providing help to B cells to support class switch recombination, affinity maturation, and B cell differentiation into long-lived plasma cells and memory cells in germinal centers (GC) in secondary lymphoid tissue. 38,39 A signature Tfh marker, CXCR5, is upregulated on naïve CD4 + T cells after antigen stimulation, permitting localization to the B cell zones of lymphoid tissue. 40,41 Mature Tfh cells expressing PD-1, ICOS and Bcl-6 provide signals for B cell survival and differentiation via CXCL13, IL-4 and IL-21 production as well as CD40L expression.…”