CD154-deficient mice reject cardiac allografts following human platelet transfusion. This is blocked by human CD154–specific 5c8. (A) PKH-26–labeled human platelets aggregate in the splenic red pulp and are also seen in the interstitium of the transplanted heart 24 hours following intravenous infusion. Shown is an H&E-stained section and its corresponding fluorescence image for spleen and cardiac allograft tissue derived from a mouse following injection of PKH-26–stained platelets. (B) CD154-KO recipients (n = 28) received human platelet transfusions followed by cardiac allografts; half were treated with 5c8. Animals that received platelets rejected (P = 0.008 versus nontransfused animals), but those pretreated with 5c8 did not (P = 0.012 versus untreated platelet-transfused animals). Infusion of platelets into WT animals (n = 5) accelerated the rate of rejection by 0.8 days (P = 0.057). Control groups C57BL/6, C57BL/6 + MR-1, and CD154KO represent the same animals described in the Figure 3 legend and are displayed in this graph for comparative purposes. (C) Cardiac allograft rejection in CD154-KO recipients that received human platelet transfusions. Magnification, ×20. (D) Allografts harvested from CD154-KO recipients treated with anti-CD154 5c8 followed by infusion of human platelets are protected from rejection and are histologically similar to cardiac allografts collected from untreated CD154-KO recipients that do not reject (not shown). Magnification, ×20.