The flavonoid Kaempferol suppresses the graft-versus-host reaction by inhibiting type 1 cytokine production and CD8+ T cell engraftment.

We have here examined the immunoregulatory effects of a natural flavonoid, Kaempferol, on T cells. Kaempferol suppressed IFN-gamma and IL-2 production but not that of IL-4 by T cells and shifted the Th1/Th2 balance into the Th2 phenotype. In C57BL/6 anti-BDF1 MLC, Kaempferol inhibited the development and expansion of type 1 effector CD8+ T cells and diminished allospecific CTL activity. Based on these in vitro results, we evaluated the effects of Kaempferol treatment on the development of C57BL/6-into-BDF1 acute graft-versus-host disease (GVHD). Brief administration of Kaempferol led to early recovery from body weight loss, increased survival, and reduced tissue injury in the liver and large intestine. Kaempferol treatment activated Th2 cells and the engraftment of donor cells and also diminished GVHD-associated antihost CTL activity. Thus, our study indicates that Kaempferol has the capacity to modulate the Th1/Th2 balance and could be useful for the treatment of cell-mediated immune diseases, such as acute GVHD.