Model for early donor T-cell migration during acute GVHD.3,-5,,111 -113 (A) Recipients of allo-BM transplant receive conditioning therapy, followed by intravenous infusion of bone marrow or peripheral blood stem cells (containing mature donor T cells). Within the first hours after transplantation, donor T cells (green) accumulate in peripheral lymphoid tissues such as LNs, Peyer patches, and spleen. (B) Alloreactive donor T cells expand in peripheral lymphoid tissues, differentiating into TH1/TC1 effectors, and producing IFN-γ, TNFα, and other cytokines (light blue arrows). (C) Circulating IFN-γ synergizes with inflammatory mediators and bacterial products released into circulation by the conditioning regimen to induce production of interferon-inducible chemokines (blue gradient arrows) by APCs and endothelial and epithelial cells in target organs. (D) Activated effector T cells follow gradients of these chemokines during early target organ infiltration (green arrows). (E) Amplification of T-cell infiltrates: donor T cells having infiltrated target organs produce T-cell–tropic chemokines CCL3, CCL4, and CCL5 (and possibly others) (pink gradient arrows). (F) Effector cells continue to follow gradients of these chemokines to infiltrate target organs (green arrows), leading to tissue pathology and clinical manifestations of GVHD, represented by green infiltrates in GI tract, liver, lung, and skin.
