Objective: Antigen-presenting cells (APC) play critical roles in establishing and maintaining peripheral tolerance. This is accomplished in part via expression of negative co-stimulatory molecules such as programmed death ligand-1 (PD-L1) on tolerogenic APC, such as immature myeloid dendritic cells (mDC). Several studies have strongly linked dysfunction of APC, including mDC, to the pathogenesis of SLE. The objective of this study was to determine whether APC expressed PD-L1 protein at normal levels during active lupus.
Methods: Peripheral blood mononuclear cells (PBMC) were isolated from 19 paediatric patients with SLE and from 17 healthy age-matched controls. PBMC from both cohorts were cultured in the absence of exogenously added stimuli, and leucocyte PD-L1 expression was measured by flow cytometry.
Results: Immature mDC and monocytes (Mo) from healthy children expressed little PD-L1 at initial isolation, but spontaneously up-regulated PD-L1 by 24 h. In contrast, both mDC and Mo from patients with active SLE failed to up-regulate PD-L1 over a 5 day time course, expressing this protein only during disease remissions.
Conclusions: These data are the first to link active lupus with reversibly decreased PD-L1 expression on professional APC, suggesting a novel mechanism for loss of peripheral tolerance in SLE.