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

在异基因造血干细胞移植后移植物抗宿主病(GVHD)和移植物抗白血病(GVL)中，我们发现了两种新的同种异体反应性T细胞激活机制。首先，除了传统的树突状细胞(DC)外，浆细胞样树突状细胞还可以完全激活同种异体反应性T细胞，从而诱导全谱GVHD。这依赖于移植前条件和MHC II类，但不依赖于PDCs中的Toll样受体(TLR)信号。第二，T细胞上的TLR信号对同种异体反应性T细胞的激活诱导移植物抗宿主病和移植物抗白血病至关重要。TLR信号对CD_4和CD_8 T细胞的激活、细胞因子的产生和杀伤活性均有重要作用。

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.