Research Article

Glucocorticoid-Induced TNFR-Related Protein Stimulation Reverses Cardiac Allograft Acceptance Induced by CD40-CD40L Blockade

Figure 3

CD4+ T cells mediate GITR-stimulated graft rejection in CD40−/− recipients. (a) Mann-Whitney survival plot of grafts was transplanted into WT+anti-CD40L (closed symbols) or CD40−/− (open symbols) recipients depleted of either CD4+ (squares) or CD8+ (circles) T cells and treated with anti-GITR mAb on days −1 and −2 prior to transplant. Significance was determined via logrank analysis. (b) H&E staining (×200) of transplants recovered either at the day of rejection or at the termination of the experiment at day 35 after transplantation. Black arrows indicate mononuclear cellular infiltrate, and yellow arrows indicate eosinophils. The inset represents 1000x magnification of infiltrate observed in CD8-depleted CD40−/− recipients. (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 total splenocytes. Significance was determined by a Student’s t-test with Welch’s correction.
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