ArrayExpress Uploader08247arrayexpress_sid7Inducible co-stimulator (ICOS) interaction with its ligand (ICOSL) is involved in several T cell effector functions. While blockade of...19890785E-GEOD-17995/profile/8773/arrayexpressuploader07cellchemokinediseasespleenveinvolumeDec.12, 2014Falserole-of-icosicosl-interaction-in-acute-gvhdE-GEOD-17995_A-AFFY-23Role of ICOS:ICOSL interaction in acute GVHDNov.23, 2014Inducible co-stimulator (ICOS) interaction with its ligand (ICOSL) is involved in several T cell effector functions. While blockade of ICOS:ICOSL interaction in chronic graft versus host disease (GVHD) seems benefi cial, results for acute GVHD remain controversial. To further elucidate its role in acute GVHD, C57BL / 6 mice were lethally irradiated and reconstituted with allogeneic spleen cells in the absence or presence of ICOSL-blocking mAb. Mice reconstituted with allogeneic spleen cells experienced severe GVHD and died untreated within 6 – 9 days after transplantation. Mice treated with an anti-ICOSL mAb starting from day 3 after transplantation gained weight again and survived for at least additional 12 days, although the treatment was already stopped at day 11 after transplantation. In contrast, the anti-ICOSL treatment starting from day 0 did not prevent GVHD. The diff erence between therapeutic (day 3) and prophylactic (day 0) anti-ICOSL treatment was independent of CD25 + CD4 + regulatory T cells since their depletion did not abrogate the therapeutic eff ect of ICOSL blockade. Microarray analysis revealed IFN- γ and chemokine up-regulation in spleen cells of prophylactically treated mice, emphasizing kinetic dependence of acute GVHD modulation via blockade of ICOS:ICOSL interaction. B6 recipients were irradiated with 10.0 Gray, administered from a 137 Cs source. Splenocytes from C3H mice were prepared as single cell suspensions in PBS, depleted of red blood cells and counted. 2 – 3 × 10^7 C3H splenocytes in a volume of 200 μl were transplanted into B6 recipients via tail vein injection (4 mice per group per experiment) 4 – 6 h after irradiation. Mice in the treatment group with anti-ICOSL mAb and their respective controls, received 500 μg mAb i. p starting at day 0 or day 3, followed by subsequent injections of 200 μg of mAb every other day. At day 4 after transplantation RNA of spleen cells was prepared and subjected to microarray analysis. Combined RNA from allogeneic transplanted mice was hybridized onto 2 independent arrays.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-17995mousehttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-17995/samples/