Moreover, early studies by Saito et al. showed that the CD28-independent graft-vs-host disease (GVHD) reaction could be significantly attenuated by treatment with anti-CD154 mAb, suggesting the superiority of the CD40-CD154 axis among non-CD28 costimulatory pathways in regulating GVHD-mediated immune responses [16]. Here, CD28 is linked to graft versus host disease.