PI3Kγ or PI3Kδ deletion and long-term allograft survival. a single dose CTLA4-Ig, injected into PI3Kγ
−/− recipients induced long-term acceptance of fully mismatched BALB/c cardiac allografts compared to the controls (MST of 41 vs. >100 days, *p < 0.05, t-test, n = 10/group). However, single dose CTLA4-Ig, injected into PI3Kδ
D910A/D910A recipients of fully mismatched BALB/c cardiac allografts showed reduced allograft survival compared to the controls (MST: 41 vs. 32 days, *p < 0.05, t-test, n = 7–10/group). b Representative examples of cardiac allograft histology at day 100 post-transplant show lower grades of acute cellular rejection in the PI3Kγ
−/− hearts treated with single dose CTLA4-Ig compared to cardiac allograft at day 28 post-transplant from WT mice treated with single dose CTLA4-Ig (n = 4/group). Inset show worse vasculopathy in the WT recipients treated with single dose CTLA4-Ig compared to PI3Kγ
−/− hearts treated with single dose CTLA4-Ig (H&E stain, scale bar 50 μm, inset scale bar 25 μm). Immunohistochemistry analysis of CD3 and FoxP3 shows fewer CD3+ infiltrating cells in the PI3Kγ
−/− hearts treated with single dose CTLA4-Ig compared to WT but relatively more FoxP3 (scale bar 50 μm). c Representative dot plots of leukocytes isolated from the allograft of PI3Kγ
−/− and WT recipients treated with single dose CTLA4-Ig show significantly less CD4+ and CD8+ infiltration in the PI3Kγ
−/− allografts compared to WT. Bar graph represents the absolute count of CD4+ and CD8+ T cells in the heart allografts of PI3Kγ
−/− and WT recipients treated with single dose CTLA4-Ig. (*p < 0.05, t-test, n = 6/group, the graphs show data as mean ± s.e.m.). d Representative examples of cardiac allograft histology at day 28 post-transplant show higher grades of acute cellular rejection in the PI3Kδ
D910A/D910A hearts treated with single dose CTLA4-Ig compared to WT mice treated with single dose CTLA4-Ig (n = 4/group). Inset show more severe vasculitis in the PI3Kδ
D910A/D910A treated with single dose CTLA4-Ig compared to WT-recipient hearts treated with single dose CTLA4-Ig (H&E stain, scale bar 50 μm, inset scale bar 25 μm). (MST mean survival time)