Recent insights into the role of the PD-1/PD-L1 pathway in immunological tolerance and autoimmunity

PD-1/PD-L1 Costimulatory Pathway-induced Mouse Islet Transplantation Immune Tolerance

“…The PD-L1 and PD-1 combination may inhibit T-cell proliferation and cytokine secretion induced by T-cell receptors, which is the negative regulatory signal of T-cell activation [12,13]. It has already been testified that targeted application of PD-L1-Ig evidently inhibits the rejection response of cardiac allografts and enhances the survival rate of allografts [14].…”

Correlation of PD-1/PD-L1 Signaling Pathway with Treg/Th17 Imbalance from Asthmatic Children

“…In this regard, the interactions between PD-1 and PD-L1 may exert functions to achieve a balanced immune response partially through Treg and Th17 immunity [37]. Therefore, the upregulated expression of PD-1, an inhibitory co-receptor, could interact with PD-L1 to suppress the activity of Treg cells toward blocking cells in the G0/G1 phase, and thereby attenuating Treg cell proliferation, cytokine secretion, and cytotoxic capacity [20, 38, 39]. In the study by Radziewicz et al [40], it was found that the PD-1/PD-L1 signaling pathway in patients with chronic hepatitis C virus negatively regulates Treg cell quantity through inhibiting STAT-5 phosphorylation, leading to a decrease in Treg cell proliferation.…”

“…Furthermore, previous studies found that the PD-1/PD-L1 signaling pathway is closely correlated with autoimmune diseases, such as systemic lupus erythematosus [22], nonobese diabetes [23], experimental allergic encephalomyelitis [24], and rheumatoid arthritis [25]. Thus, targeting the PD-1/PD-L1 signaling pathway has become a new insight for investigating the treatment of autoimmune diseases [20]. A previous study conducted by Wang et al [26] suggested that PD-1 was involved in the modulation of Treg function in patients with melanoma.…”

“…Programmed cell death-1 (PD-1) and it ligand PD-L1, as members of CD28/ B7 protein family, participate in the transmission of the T lymphocyte co-stimulatory signal and act as a key element in regulating T-cell immune response and T-cell-mediated peripheral immune tolerance [20, 21]. Furthermore, previous studies found that the PD-1/PD-L1 signaling pathway is closely correlated with autoimmune diseases, such as systemic lupus erythematosus [22], nonobese diabetes [23], experimental allergic encephalomyelitis [24], and rheumatoid arthritis [25].…”

TCR stimulation without co-stimulatory signals induces expression of “tolerogenic” genes in memory CD4 T cells but does not compromise cell proliferation

“…To ensure immune tolerance to self, many negative regulatory mechanisms exist to control the T cell survival/function and continuously tolerize self-reactive T cells in the periphery. Those negative regulatory mechanisms involve some cell subsets (e.g., Foxp3 + regulatory T cells) (Cretney et al, 2013;Bilate and Lafaille, 2012), released soluble factors (e.g., TGF-␤, IL-10), (Chen et al, 2003;Taylor et al, 2006) and cell surface molecules (e.g., CTLA4, PD-1) (Scalapino and Daikh, 2008;Gianchecchi et al, 2013;Pentcheva-Hoang et al, 2009).…”