Regulation of T:B cell interactions by the inducible costimulator molecule: does ICOS "induce" disease?

The Inducible Costimulator molecule (ICOS), a member of the CD28 family of costimulatory molecules, was identified in 1999 as a molecule expressed primarily on activated human T cells. Induced upon activation, ICOS appears to be an ideal target for modifying T-cell-mediated immune responses. ICOS was also found to be highly expressed on germinal center T cells, suggesting that ICOS was involved in T:B cell interactions. While ICOS has subsequently been shown to be important for both Th1 and Th2 cell activation and effector function, a central role for ICOS in the generation and maintenance of humoral immunity is emerging. In this review, we summarize the evidence that the level of ICOS expression regulates T-cell-dependent B cell responses and propose a model for the role of ICOS in diseases characterized by dysregulated humoral immunity.