ICOS ligand costimulation is required for T-cell encephalitogenicity

The interaction of ICOS with its ligand on APC provides a costimulatory sig nal to previously activated T-cells. In these studies, we blocked the ICOS: ICOS ligand interaction with ICOS-Ig during the in vitro activation of AMP- reactive transgenic CD4(+) T-cells. The presence of ICOS-Ig in these cultur es inhibited the ability of the transgenic T-cells to transfer EAE, althoug h they entered the brains of the recipient mice. ICOS-Ig increased apoptosi s in the transgenic T-cells, especially in the memory population. This enha nced apoptosis was accompanied by an increase in the BAX/BCL-2 mRNA ratio. ICOS-Ig did not prevent IL2 production, demonstrating that IL-2 production is ICOS ligand independent. IFN-gamma and IL-10 production by the transgeni c T-cells, however, was suppressed. Finally, ICOS-Ig injection into mice af ter the first signs of EAE ameliorated clinical disease. Therefore, ICOS-Ig provides a signal distinct from CD28 costimulation that is required for th e activation and viability of encephalitogenic T-cells. (C) 2001 Academic P ress.