IL-15–mediated exacerbation of acute GVHD is dependent upon CD8⁺ or CD4⁺ T lymphocytes. B6D2F1 mice received transplants of 5 × 10⁶ wt B6 splenic T cells and 1 × 10⁷ BM cells from either wt B6 or IL-15 tg B6 mice. Survival of recipients of IL-15 tg B6 allogeneic BM cells treated with control rat IgG (•, MST = 13 days, n = 7) or depleting doses of rat antimouse CD4 (□, MST = 28 days, n = 5), CD8 (▵, MST = 64 days, n = 5), or both (○, 100% survival, n = 5). Median survival time for B6D2F1 mice that received transplants of 5 × 10⁶ wt B6 splenic T cells, and 1 × 10⁷ BM cells from wt B6 mice treated with control rat IgG was 34 days (not shown). □ versus •, P = .002; ▵ versus •, P = .002; ○ versus •, P = .002; and □ versus ▵, P = .048.