Revisiting PD-1/PD-L pathway in T and B cell response: Beyond immunosuppression

The regulation of T cell response depends on co-inhibitory pathways that serve to control immune-mediated tissue damage and resolve inflammation by modulating the magnitude and duration of immune response. In this process, the axis of T-cell-expressed programmed death-1 (PD-1) and its ligands (PD-L1 and PD-L2) play a key role. While the PD-1/PD-L pathway has received considerable attention for its role in the maintenance of T cell exhaustion in cancer and chronic infection, the PD-1/PD-L pathway also plays diverse roles in regulating host immunity beyond T cell exhaustion. In this review, we will discuss emerging concepts in co-stimulatory functions of PD-1/PD-L pathway on T cell- and B cell response and explore the potential underlying mechanisms. In addition, based on the elevated expression of PD-1 and its ligands in local inflamed tissues, we further discussed the role of PD-1/PD-L pathway in autoimmune diseases.