Cognate interactions are required for maximal CD4-mediated GVL. B6 mice were irradiated and reconstituted with T-cell-depleted C3H.SW BM, wild-type, or IA^b-/- mCP-CML, with or without 6 × 10⁶ C3H.SW CD4⁺ T cells. Survival was significantly reduced in recipients of IA^b-/- mCP-CML and CD4 cells as compared with wt mCP-CML and CD4 cells. Each panel is an independent experiment. Experiment 1: IA^b mCP-CML BM alone versus IAb mCP-CML BM/CD4, P < 0.11; wt mCP-CML BM/CD4 versus IA^b-/- mCP-CML BM/CD4, P < .0001. Experiment 2: IA^b mCP-CML BM alone versus IA^b mCP-CML BM/CD4, P < .02; wt mCP-CML BM/CD4 versus IA^b-/- mCP-CML BM/CD4, P < .0001.