The immunological synapse for B-cell memory: the role of the ICOS and its ligand for the longevity of humoral immunity

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Abstract
The ICOS is one of the many costimulatory molecules of T cells. Recently, the authors discovered that the homozygous loss of the ICOS in humans presents as common variable immunodeficiency, the most prevalent treated primary immunodeficiency in man. Therefore, the ICOS is after CD40 and CD40-ligand deficiency the third costimulatory molecule for which a human disease has been described. The description of ICOS deficiency made it necessary to review the vast amount of knowledge from experimental models in the light of a new clinical immunodeficiency phenotype. To this end, after introducing the ICOS and its ligand and comparing the murine and human ‘knockout’, the role of the ICOS in parasitic and viral infections, asthma, autoimmunity, transplantation immunology, and tumor surveillance will be discussed. The focus of this review is the interaction between the ICOS and its ligand, which is essential for T cell dependent B cell responses.