Model for the role of IFNγR signaling in T-cell trafficking and GVHD. Naive Tconvs and Tregs become activated by host APCs because of MHC mismatch. (1) Activated Tconv secrete IFNγ (2) that will initiate the IFNγR signaling, which in turn up-regulates CXCR3 and other unknown mediators of T-cell trafficking on both Tconvs and Tregs. (3) CXCR3+ T cells migrate to the CXCR3 ligands-expressing GVHD target organs (4) where activated Tconv are destructive but suppressed in the presence of activated Tregs. (5) When Tconvs fail to secrete IFNγ (IFNγ^−/− Tconv), Tregs will not activate IFNγR signaling, thereby failing to migrate to the same sites of inflammation as IFNγ^−/− Tconv. This will result in more severe GVHD than WT Tconv. Likewise, when Tregs are defective in up-regulating CXCR3 because of the lack of IFNγR, the same result will be observed. T_n: naive Tconv, T_act: activated Tconv, _nT_reg: naive Tregs, _aT_reg: activated Tregs, M: MHC molecules, T: T-cell receptors, R: IFNγR, 3: CXCR3, γ: IFNγ.