Step 4: T-cell trafficking. In rodents, secondary lymphoid organs are known to facilitate GVHD initiation. In both rodents and humans, GVHD tissue injury requires migration of such activated donor T cells into GVHD target organs that is orchestrated by chemokines, selectin, and adhesion molecules. An example of the homing process into the skin is depicted. The red boxes below the mouse and the human recipient serve to highlight distinct features between these species. Question marks denote uncertain conclusions. In the center red box, we note that clinical translational approaches to prevent GVHD by blocking individual chemokine/receptor interactions may be difficult due to known redundancies that exist for many pathways.