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. 2018 Dec 21;9:3061. doi: 10.3389/fimmu.2018.03061

Figure 2.

Figure 2

Diagram of PD-L1-mediated signaling regulation of T cell metabolism, proliferation and tolerance in lymphoid and GVHD target tissues. In lymphoid tissue, PD-L1/CD80 interaction is dominant and leads to T cell expansion to promote GVL effects. Signaling either through PD-L1 or CD80 via DC:T or T:T interactions leads to increased glycolysis, proliferation, expansion, and IFN-gamma production. In GVHD target tissues, PD-L1 expressed by parenchymal cells interacts with PD-1 expressed by donor T cells and induces their anergy, exhaustion or apoptosis (depending on the microenvironment) to establish T cell tolerance and prevent GVHD. IFN-gamma produced by donor T cells can augment PD-L1 expression and PD-L1/PD-1 interaction reprograms donor T cells toward a quiescent metabolic phenotype. On the other hand, autocrine or paracrine IL-2 signaling can overcome PD-L1/PD-1 interaction to maintain donor T cell effector function.