OBJECTIVE: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by B cell hyperactivity and defective T cell functions, including 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 with 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 proliferation of T cells in the mixed lymphocyte reaction (MLR), which was assessed by measurement of tritiated thymidine incorporation in studies using granulocyte-macrophage colony-stimulating factor-activated, DC-enriched APC. Correlations between DC counts and phenotype and clinical parameters in SLE patients were determined. RESULTS: Lin-, HLA-DR+, CD4+ DC were, on average, 50% less frequent in SLE patients than in controls. Moreover, among DC, the proportions of B7+ and CD40+ 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 from SLE patients revealed a diminished T cell-stimulatory capacity in both the allogeneic and the antigen-specific MLR, as compared with healthy individuals. Although the frequencies of DC were weakly inversely correlated with disease activity and/or current treatment protocols, our data suggest a disease-intrinsic defect. CONCLUSION: The considerable alterations of DC and DC subsets in SLE patients may contribute to the pathogenic mechanisms involved in the disease.
OBJECTIVE:Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by B cell hyperactivity and defective T cell functions, including 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 SLEpatients in comparison with healthy controls. METHODS: Samples from 25 SLEpatients and 15 healthy controls were studied. To identify DC, peripheral blood mononuclear cells were double stained with 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 proliferation of T cells in the mixed lymphocyte reaction (MLR), which was assessed by measurement of tritiated thymidine incorporation in studies using granulocyte-macrophage colony-stimulating factor-activated, DC-enriched APC. Correlations between DC counts and phenotype and clinical parameters in SLEpatients were determined. RESULTS: Lin-, HLA-DR+, CD4+ DC were, on average, 50% less frequent in SLEpatients than in controls. Moreover, among DC, the proportions of B7+ and CD40+ cells were reduced and, in particular, the CD11c+ subset was reduced by an average of 80% in SLEpatients. Functional analysis of DC-enriched APC from SLEpatients revealed a diminished T cell-stimulatory capacity in both the allogeneic and the antigen-specific MLR, as compared with healthy individuals. Although the frequencies of DC were weakly inversely correlated with disease activity and/or current treatment protocols, our data suggest a disease-intrinsic defect. CONCLUSION: The considerable alterations of DC and DC subsets in SLEpatients may contribute to the pathogenic mechanisms involved in the disease.
Authors: K Migita; T Miyashita; Y Maeda; H Kimura; M Nakamura; H Yatsuhashi; H Ishibashi; K Eguchi Journal: Clin Exp Immunol Date: 2005-10 Impact factor: 4.330
Authors: Pui Y Lee; Jason S Weinstein; Dina C Nacionales; Philip O Scumpia; Yi Li; Edward Butfiloski; Nico van Rooijen; Lyle Moldawer; Minoru Satoh; Westley H Reeves Journal: J Immunol Date: 2008-04-01 Impact factor: 5.422
Authors: Ilan Ben-Zvi; Cynthia Aranow; Meggan Mackay; Anfisa Stanevsky; Diane L Kamen; L Manuela Marinescu; Christopher E Collins; Gary S Gilkeson; Betty Diamond; John A Hardin Journal: PLoS One Date: 2010-02-16 Impact factor: 3.240