Novel mechanisms of alloreactive T-cell activation in GVHD and GVL

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We have identified two novel mechanisms of alloreactive T-cell activation in graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) after allogeneic hematopoietic stem cell transplantation. First, besides conventional dendritic cells (DCs), plasmacytoid DCs can also fully activate alloreactive T cells to induce full spectrum of GVHD. This is dependent on pretransplant conditioning and MHC class II, but independent of toll-like receptor (TLR) signaling in pDCs. Second, TLR signaling in T cells are critical for activation of alloreactive T cells to induce GVHD and GVL. TLR signaling is important for activation, cytokine production, and cytolytic activity of both CD4+ and CD8+ T cells.