Glucocorticoid-Induced TNFR-Related Protein Stimulation Reverses Cardiac Allograft Acceptance Induced by CD40-CD40L Blockade
Figure 1
GITR stimulation induces graft rejection in WT+anti-CD40L and CD40−/− allograft recipients. (a) Mann-Whitney survival plot of grafts transplanted into WT (circles), WT+anti-CD40L (triangles), or CD40−/− recipients (squares). All recipients were treated with 1 mg of IgG isotype control (open symbols, dotted line), anti-GITR mAb (closed symbols, solid line) on days −2 and −1 relative to transplantation, or anti-GITR mAb that was administered at days 29 and 30 after transplant (open symbols, solid lines), and mice were observed until 50 days after transplant. Significance was determined via logrank analysis . (b) Hematoxylin and eosin (H&E; ×200) staining of cardiac allografts recovered from recipients at the day of rejection or at 35 days after transplant (controls). Recipients were treated with either 1 mg of rat IgG isotype (control) or anti-GITR mAb (GITR stim) on days −2 and −1 relative to transplant. Arrows indicate mononuclear cellular infiltrate. (c) Recipient splenocytes were harvested and processed at the time of rejection or at 35 days after transplant for ELISPOT assays, and primed, donor-reactive IFN-γ and IL-4 producing cells were quantified as the number of spots/106 splenocytes. Significance was determined by a Student’s t-test with Welch’s correction.
