Notch signaling blockade with a γ-secretase inhibitor mitigates T-cell expansion in chimeras with Ik^−/− host APCs. WT B6 Ly5.2 animals were lethally irradiated with 11 Gy and infused with 5 × 10⁶ BM cells and 5 × 10⁶ splenocytes from syngeneic Ly5.1 WT B6 or Ik^−/− B6 donors. Four months later, these chimeras [B6 → B6Ly5.2] or [Ik^−/− → B6Ly5.2] chimeras were re-irradiated with 9 Gy and transplanted with 2 × 10⁶ CD90⁺ T cells along with 5 × 10⁶ BM cells from either syngeneic B6 (n = 4/group) or allogeneic MHC-matched, multiple miHA-mismatched C3H.sw donors (n = 8/group). They were also injected IP with the γ-secretase inhibitor DAPT (5 μg/kg) on days −1, +1, and +3 after BMT. (A) The animals were analyzed for GVHD with as shown by body weight loss at day 10. Shown are C3H.sw → [Ik^−/− → B6Ly5.2] (○) versus C3H.sw → [Ik^−/− → B6 Ly5.2] + DAPT (□) (n = 8 mice/group, P < .05) and C3H.sw → [B6 → B6Ly5.2] (●) versus C3H.sw → [B6 → B6 Ly5.2] + DAPT (■) (n = 8 mice/group, P = not significant). (B) Donor CD4⁺ and CD8⁺ T-cell expansion at day 10. Shown are C3H.sw → [Ik^−/− → B6Ly5.2] (○) versus C3H.sw → [Ik^−/− → B6 Ly5.2] + DAPT (□) (P < .05) and C3H.sw → [B6 → B6Ly5.2] (●) versus C3H.sw → [B6 → B6 Ly5.2] + DAPT (■) (n = 8 mice/group, P = not significant).