We recently demonstrated that GVHD in that humanized model is caused by a limited number of CD4 and CD8 xeno- as well as probably allo- reactive T-cell clones that expand via activation of the TCR, costimulation, IL-2/STAT5, mTOR, and Aurora kinase A pathways and differentiate into effector cells in GVHD-target organs, secreting high amounts of interferon gamma (IFNγ) and TNFα (31). Here, CD4 is linked to graft versus host disease.