Alterations of dendritic cells in systemic lupus erythematosus - Phenotypic and functional deficiencies

Objective. Systemic lupus erythematosus (SLE) is a systemic autoimmune dise ase characterized by B cell hyperactivity and defective T cell functions, i ncluding interleukin-2 production and proliferation. The defects in T cell function may result from underlying defects in antigen-presenting cell (APC ) function. The present study was undertaken to investigate phenotypic and functional characteristics of peripheral blood dendritic cells (DC), as the most potent APC, in SLE patients in comparison with healthy controls. Methods. Samples from 25 SLE patients and 15 healthy controls were studied. To identify DC, peripheral blood mononuclear cells were double stained wit h monoclonal antibodies against lineage marker (lin)-specific molecules CD3 , CD19, CD14, and CD16, versus CD4. DC were characterized phenotypically by flow cytometry. The stimulatory capacity of DC was determined by prolifera tion of T cells in the mixed lymphocyte reaction (MLR), which was assessed by measurement of tritiated thymidine incorporation in studies using granul ocyte-macrophage colony-stimulating factor-activated, DC-enriched APC. Corr elations between DC counts and phenotype and clinical parameters in SLE pat ients were determined. Results. Lin-,HLA-DR+,CD4+ DC were, on average, 50% less frequent in SLE pa tients than in controls. Moreover, among DC, the proportions of B7+ and CD4 0+ cells were reduced and, in particular, the CD11c+ subset was reduced by an average of 80% in SLE patients. Functional analysis of DC-enriched APC f rom SLE patients revealed a diminished T cell-stimulatory capacity in both the allogeneic and the antigen-specific MLR, as compared with healthy indiv iduals. Although the frequencies of DC were weakly inversely correlated wit h disease activity and/or current treatment protocols, our data suggest a d isease-intrinsic defect. Conclusion. The considerable alterations of DC and DC subsets in SLE patien ts may contribute to the pathogenic mechanisms involved in the disease.