In acute graft-versus-host disease (GVHD), both human and murine experimental evidence demonstrates that co-blockade using tetravalent CTLA-4-Ig and LAG-3-Ig could synergistically suppress T cell responses, prevent acute GVHD, and decrease GVHD fatality rates as well [86]. Here, CTLA4 is linked to acute graft versus host disease.