CD4⁺ T_Ns and T_EMs require cognate interactions with MHCII⁺ mCP-CML cells to mediate GVL. B6 mice were irradiated and reconstituted with T cell–depleted B6^bm12 BM, wt B6, or IA^bβ^−/− mCP-CML, with no T cells or with 5 × 10⁵ T_N or 10⁶ T_EM B6^bm12 CD4 cells. (A) Survival data from 1 of 2 similar experiments; P = .002 for recipients of IA^bβ^−/− mCP-CML and T_EMs versus wt B6 mCP-CML and T_EMs; P = .004 comparing recipients of IA^bβ^−/− mCP-CML and T_Ns versus wt B6 mCP-CML and T_Ns. (B) Numbers of NGFR⁺ cells in the peripheral blood of mice that underwent transplantation taken at different time points. At day 9, peripheral blood was harvested from only 2 of 8 recipients of wt mCP-CML and T_Ns and 2 of 4 recipients of IA^bβ^−/− mCP-CML and T_Ns, as we were concerned that the remainder might not tolerate the procedure due to the severity of GVHD. Comparing recipients of wt mCP-CML and T_Ns versus T_EMs, P < .04 on days 15, 22, and 39 and P > .3 on days 37 and 54. (C) Spleen weight of each recipient after death or killing at day + 50. P > .4 comparing spleen weights of recipients of IA^bβ^−/− mCP-CML and either T_Ns or T_EMs versus no T cells; P < .008 comparing spleen weights of recipients of wt mCP-CML and either T_Ns or T_EMs versus no T cells. Horizontal bars represent mean values.