Notch inhibition prevents lethality in a nonirradiation semiallogeneic transplantation model. (A) Experimental design. Splenocytes (4 × 107) from WT or DNMAML B6 mice were transplanted into unirradiated B6xDBA F1 (BDF1) recipients. BDF1 recipients (H-2b/d) are tolerant to the infused B6 cells (H-2b), but donor T cells mount a potent alloreactive response against host H-2d antigens. (B) Improved overall survival of BDF1 recipients receiving DNMAML B6 T cells (n =9 in each group; P < .01). (C) Tracking of CFSE-labeled donor-derived T cells at day 5 after transplantation into BDF1 recipients. CFSElow cells are alloantigen-specific in this model. (D) Modest decrease in the expansion of alloreactive CD4+ and CD8+ DNMAML T cells at day 5. (E) Enhanced accumulation of DNMAML CD4+ and CD8+ alloreactive T cells in the spleen and target BM at day 17 after transplantation. *P < .05, **P < .01 (2-tailed unpaired Student t test).