A method of preventing the development of GvHD or reducing the severity of GvHD in a mammalian subject receiving an allogeneic hematopoietic stem cell (HSC) transplant includes administering to the subject a pharmaceutical composition comprising an active agent that inhibits the biological activity or expression of hypoxia-inducible factor-1a (HIF-1a) or hypoxia-inducible factor-2a (HIF-2a), wherein the active agent is administered in an amount effective for preventing or reducing the severity GvHD in the subject.
