CD28 and ICOS: similar or separate costimulators of T cells?

Numerous studies have revealed that the B7.1/B7.2-CD28 and B7RP-1-ICOS (Inducible COStimulator) pathways provide crucial costimulatory signals to T cells. We have compared the contribution of these pathways during primary and effector responses, in vitro and in vivo, molecularly as well as functionally. This comparison between CD28 an ICOS after initiation of T cell activation demonstrates that both CD28 and ICOS function similarly during expansion, survival and differentiation of T cells and that both CD28 and ICOS are necessary for proper IgG responses. The major differences between CD28 and ICOS are differences in expression of both receptors and ligands, and the fact that CD28 induces IL-2 production, whereas ICOS does not. In addition, ICOS is more potent in the induction of IL-10 production, a cytokine important for suppressive function of T regulatory cells. All data available at present indicate that both molecules are very suitable candidates for immunotherapy, each in their own unique way.