Defective programmed death ligand-1 (PD-L1) expression on monocytes from systemic lupus erythematosus (SLE) patients can be corrected by a soluble T lymphocyte factor (99.15)

Abstract

Abstract PD-L1 is an inhibitory protein expressed on monocytes (Mo) to maintain peripheral T cell tolerance. We previously reported deficient expression of PD-L1 on Mo from patients with active SLE. To investigate the mechanisms for dysregulated PD-L1 expression in SLE we isolated peripheral blood mononuclear cells (PBMC) from juvenile SLE patients and age-matched controls. PD-L1 expression was measured by flow cytometry and realtime quantitative RT-PCR. Cytokines were analyzed by Luminex. We found that PD-L1 expression on SLE Mo was significantly induced by PBMC or CD4+ T lymphocytes from healthy subjects, and also by supernatant from healthy PBMC. Conversely, PD-L1 expression was decreased in healthy donor Mo by addition of SLE PBMC or supernatant. SLE cells had an increased rate of apoptosis, and inhibition of caspase activity led to decreased apoptosis and upregulation of PD-L1. PD-L1 mRNA expression did not correlate with protein expression. Among 15 cytokines tested, only IL-2 and IL-10 were elevated in plasma of SLE patients with active disease. These results suggest that expression of PD-L1 in juvenile SLE is controlled by caspases at the protein level via soluble factors normally produced by T lymphocytes. Abnormal T lymphocyte activity in SLE may prevent induction of PD-L1, leading to loss of peripheral tolerance. Supported by the Lupus Foundation and the Lupus Research Institute