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Rheumatology Advance Access originally published online on July 23, 2008
Rheumatology 2008 47(9):1335-1341; doi:10.1093/rheumatology/ken256
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Active systemic lupus erythematosus is associated with failure of antigen-presenting cells to express programmed death ligand-1

N. Mozaffarian1,2, A. E. Wiedeman2 and A. M. Stevens2,3

1Division of Rheumatology, Department of Medicine, University of Washington, 2Research Center for Immunity and Immunotherapies, Children's Hospital and Regional Medical Center and 3Division of Rheumatology, Department of Pediatrics, University of Washington, Seattle, WA, USA.

Correspondence to: N. Mozaffarian, Seattle Children's Hospital Research Institute, 1900 Ninth Avenue, 7th floor, Seattle, WA 98101, USA. E-mail: neely.mozaffarian{at}seattlechildrens.org


  Abstract

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.

KEY WORDS: Systemic lupus erythematosus, Human, Antigen-presenting cell, Monocyte, Myeloid dendritic cell, Programmed death ligand-1, Co-stimulation

Submitted 29 January 2008; revised version accepted 13 June 2008.
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