ICOS deficiency protects from histopathologic GVHD damage without affecting homing to target organs. Lethally irradiated (1300 cGy split) C3FeB6F1 recipients received transplants with WT B6 TCD allo-HSCs (5 × 10⁶) and splenic T cells (1 × 10⁶) from WT or ICOS^-/- B6 donors. Each group contained 6 to 8 animals. (A-C) Histopathologic analysis of GVHD target organ damage. Recipients were killed on day 14 (liver, small and large bowel), and day 21 (skin) target organs were collected. (A-B) H&E-stained slides of liver, intestines, and skin were analyzed and scored for GVHD histopathologic damage. The graphics represent the average scores ± SEM. ⋆Statistical analyses: liver, P < .01; small bowel (S.B.), P < .01; large bowel (L.B.), P < .05; (B) skin, P < .008. (C) Skin histopathology in recipients of WT (left panel) and ICOS^-/- T cells (right panel). Arrowheads denote apoptotic epidermal cells associated with infiltration by effector lymphocytes. Both qualitatively and quantitatively, epidermal injury was more severe in recipients of ICOS^-/- T cells (× 400). (D) Thymic cellularity. Recipients were killed at day 21, thymi were harvested, and cells analyzed by flow cytometry. Data are shown as the average of absolute T-cell numbers ± SEM. Statistical analysis: no difference. (E) Donor T-cell content in liver. Recipients were killed at day 21, livers were harvested, and T cells were isolated and analyzed by flow cytometry. Data are shown as the average of absolute T-cell numbers ± SEM. Statistical analysis: no difference. (F) Donor T-cell content in gut. Recipients were killed at day 21, small intestines were harvested, and T cells were isolated and analyzed by flow cytometry. Data are shown as the average of absolute T-cell numbers ± SEM. Statistical analysis: no difference. Day 14 harvest data are representative of 1 experiment of 2 independent experiments (n = 6 to 8 animals). Day 21 harvest data are from 1 independent experiment (n = 6 to 8 animals).