Regulation of T follicular helper cells by ICOS

T follicular helper (TFH) cells are gatekeepers of the humoral immune response. Without help from this CD4+ T cell subset, B cells cannot differentiate into high-affinity memory B cells and antibody-producing long-lived plasma cells which are the basis of protective immune responses. At the same time, dysregulated TFH cell responses are causative for many autoimmune disorders (reviewed in [1]). The inducible T cell costimulator ICOS, which is structurally and functionally related to CD28, has been known for many years as an important regulator of TFH cells. ICOS knock-out mice as well as ICOS-deficient patients have only few TFH cells and very small germinal centers upon immunization, which results in severely compromised antigen-specific immunoglobulin levels and the phenotype of common variable immunodeficiency