Loss of IL-21 signaling on donor T cells does not eliminate GVL activity. Lethally irradiated Balb/c recipients were injected with T cell–depleted bone marrow and 10⁵ A20 lymphoma cells on day 0. Subgroups received 2 × 10⁶ CD25⁻ T cells from wt or IL-21R^−/− mice also on day 0. (A) Tumor growth was monitored by luciferase imaging on days 8, 20, and 32 after BMT. (B) Photon counts of BM-only recipients (*), recipients of BM + wt T-effector cells (▾), and BM + IL-21^−/− cells (▿) on days 8, 20, and 32. (C) Survival of lethally irradiated Balb/c recipients injected with T cell–depleted bone marrow alone (*) or together with 2 × 10⁶ CD25⁻ T cells from wt B6 mice treated with irrelevant (irr) IgG (▾) or aIL-21 Ab (▵), or with 2 × 10⁶ CD25⁻ T cells from IL-21^−/− (▿) or perforin^−/− mice treated with irr IgG (♦) or aIL-21 Ab (◇; P < .001 for ▾ versus ▿, ▾ versus ♦, and ▾ versus ◇; P < .05 for ▾ versus ▿, ▿ versus ◇; P = ns for all others). (D) Survival of the same recipients as in panel C, but coinjected with 10⁵ A20 lymphoma cells (P ≤ .001 for ▾ versus ▿; P < .05 for ▾ versus ▵, ♦ versus ◇, and ▾ versus ♦; P = ns for all others). Data from 2 experiments with a total of 8 (A-B) and 7 (C-D) mice per group.