Regulation of CD4 T Cell Activation and Effector Function by Inducible Costimulator (ICOS)

Inducible costimulator (ICOS), a member of the CD28 family of costimulatory molecules, is upregulated on the surface of T cells following T cell activation and upon binding to its ligand (ICOSL), initiates a cascade of events that can shape key aspects of the immune response. Although initial studies focused on determining the role of ICOS in Th1 versus T helper 2 (Th2) responses, new insights into its biology have revealed the contribution of ICOS to germinal center formation and isotype switching, as well as its relevance to the fate and function of effector and regulatory CD4(+) T cells in the response against self (i.e., tumors) and non-self (i.e., bacterial, worm, and viral infections). This multiplicity of roles positions ICOS at the center of attention for immunotherapy where manipulation of this pathway could lead to novel approaches in the treatment of human diseases.