Suppression of Negative Immune Regulators PD-1 and PD-L1 Expression on Lymphocytes by Inflammatory Cytokines.

The strength and duration of lymphocyte activation is determined by the net effect of positive and negative regulatory co-signaling molecules. The inhibitory receptor PD-1 and its ligand PD-L1 are both expressed on activated lymphocytes. Mice deficient of PD-1 or PD-L1 demonstrate lymphocyte hyperactivity and are prone to autoimmunity. We have shown that the expression and function of PD-1 on activated B lymphocytes can be down-regulated by certain inflammatory cytokines, rendering them resistant to PD-L1 mediated suppression. Here we further report that both PD-1 and PD-L1 expression on activated T lymphocytes can be down-regulated in a similar fashion. Thus, in addition to stimulating positive regulators, inflammatory cytokines may boost immune responses and break self-tolerance by inhibiting a negative regulator on T and B lymphocytes. Our findings may indicate a potential mechanism for the link between chronic inflammation and autoimmunity.