Figure 1. T cell-specific Notch inhibition delays the rejection of heart allografts.
(A) Vascularized cardiac BALB/c allografts were established in wild-type C57BL/6 recipients (WT, n=8) or in C57BL/6 mice expressing the pan-Notch inhibitor DNMAML in mature T cells (DNMAML, n=9). Arrows indicate hearts still functioning at the time of sacrifice. Survival of the heart allografts was prolonged in DNMAML recipients (p<0.0001, % survival scored based on abdominal palpation); (B) Decreased numbers of graft-infiltrating cells (GICs) in DNMAML as compared to WT recipients at the time of rejection (n=8-9/group); (C) Histology showing cellular infiltrates in the rejected hearts (WT: day 7; DNMAML: day 11); (D) Enumeration of donor-reactive cells producing IFNγ, IL-4 and IL-17 in the spleen of transplant recipients, showing decreased IFNγ-producing cells in DNMAML vs. WT recipients (p=0.0002); (E) Quantification of donor-reactive IgG in the serum of WT and DNMAML recipients. DNMAML did not prevent the emergence of these antibodies (p=0.1226 for WT vs. DNMAML IgG). Naïve WT and DNMAML sera served as negative controls.