Follicular Helper T Cells

Abstract Follicular helper T (Tfh) cells are a subset of helper T cells with specialised functions to support high-affinity and long-term antibody responses. Tfh cells express high levels of transcription factor Bcl6, chemokine receptor CXCR5, cytokine IL-21 and costimulatory receptor PD-1 and ICOS, showing a phenotype distinct from other helper T-cell subsets. The differentiation and function of Tfh cells are regulated by a unique molecular program orchestrated by the transcriptional factor Bcl6. The knowledge of Tfh cells provides new insights into the physiopathology of many human diseases, including immunodeficiency, autoimmune disease, infection and cancer. Key Concepts Tfh cells are a helper T-cell subset. Tfh cells regulate antibody response. CXCR5 is an important functional marker for Tfh cells. The ICOS–Bcl6 pathway critically regulates the differentiation of Tfh cells. Certain primary immunodeficiencies show defects in Tfh cells. Aberrant and/or excessive Tfh function promotes autoimmune diseases.