Phenotypic and functional deficiencies of monocyte-derived dendritic cells in systemic lupus erythematosus (SLE) patients

Köller, Marcus; Zwölfer, Bettina; Steiner, Günter; Smolen, Josef S.; Scheinecker, Clemens

doi:10.1093/intimm/dxh160

Cited by 47 publications

(45 citation statements)

References 31 publications

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“…Confirming a previous study (54), no morphologic differences in the capacity of monocytes to differentiate into DCs were found between SLE and controls, using light and fluorescent microscopy ( Fig. 1).…”

Section: Myeloid Lupus Dcs Display Abnormal Levels Of Differentiationsupporting

confidence: 91%

Aberrant Phenotype and Function of Myeloid Dendritic Cells in Systemic Lupus Erythematosus

Ding

Mehta

McCune

et al. 2006

The Journal of Immunology

133

106

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Systemic lupus erythematosus (SLE) is characterized by a systemic autoimmune response with profound and diverse T cell changes. Dendritic cells (DCs) are important orchestrators of immune responses and have an important role in the regulation of T cell function. The objective of this study was to determine whether myeloid DCs from individuals with SLE display abnormalities in phenotype and promote abnormal T cell function. Monocyte-derived DCs and freshly isolated peripheral blood myeloid DCs from lupus patients displayed an abnormal phenotype characterized by accelerated differentiation, maturation, and secretion of proinflammatory cytokines. These abnormalities were characterized by higher expression of the DC differentiation marker CD1a, the maturation markers CD86, CD80, and HLA-DR, and the proinflammatory cytokine IL-8. In addition, SLE patients displayed selective down-regulation of the maturation marker CD83 and had abnormal responses to maturation stimuli. These abnormalities have functional relevance, as SLE DCs were able to significantly increase proliferation and activation of allogeneic T cells when compared with control DCs. We conclude that myeloid DCs from SLE patients display significant changes in phenotype which promote aberrant T cell function and could contribute to the pathogenesis of SLE and organ damage.

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Section: Myeloid Lupus Dcs Display Abnormal Levels Of Differentiationsupporting

confidence: 91%

Aberrant Phenotype and Function of Myeloid Dendritic Cells in Systemic Lupus Erythematosus

Ding

Mehta

McCune

et al. 2006

The Journal of Immunology

133

106

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“…However, recent data obtained by Ding et al [17] and Decker et al [16] was more comparable to our findings. Different results in the more recent studies may have occurred due to younger DC populations (days 5-7 versus day 8 in the Koller et al study [14]), or maturation effects from the use of fetal bovine serum (FBS) to generate cells [26]. In addition, as shown in this study, a significant portion of patients may have iDC surface CD86 and MHC class II levels that are lower or comparable to those in healthy individuals.…”

Section: Discussionmentioning

confidence: 52%

“…This hypothesis is consistent with the accelerated AMLR and HMLR response seen in most SLE patients. Again, Koller et al [14] found an AMLR decrease in lupus patients. However, they used relatively ''old'' iDC that may have exhausted their extra maturation capacity.…”

Section: Discussionmentioning

confidence: 96%

“…Blood-derived myeloid DC were reported to have low expression [15]. Koller et al [14] reported comparable expression of CD86 and even lower expression of MHC class II. However, recent data obtained by Ding et al [17] and Decker et al [16] was more comparable to our findings.…”

Section: Discussionmentioning

confidence: 99%

“…It was suggested that patients with SLE have increased differentiation of precursor cells into monocyte-derived DC due to the effect of IFN-a produced by pDC [13]. Myeloid DC were found to be either spontaneously hypo- [14,15] or hyperactivated [16,17] with a decreased [14,15] or increased [17] mixed lymphocyte reaction (MLR). However, their capacity and function following apoptotic cell interaction was not examined.…”

Section: Introductionmentioning

confidence: 99%

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Altered dendritic cells with tolerizing phenotype in patients with systemic lupus erythematosus

et al. 2008

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Earlier we showed the generation of tolerizing human monocyte-derived DC following interaction with iC3b-opsonized apoptotic cells. In this study we examine the generation of DC with our previously described tolerogenic phenotype in patients with the systemic autoimmune disease systemic lupus erythematosus (SLE). Monocyte-derived DC were generated in 71 SLE patients, characterized, and then tested for clearance of iC3b-opsonized 1,1 0 -dioctadecyl-3,3,3 0 ,3 0 -tetramethyl-indocarbocyanineperchlorate-stained apoptotic cells using flow cytometry, and for autologous T-cell activation using autologous mixed lymphocyte reaction (AMLR), at the same time as controls. Compared with healthy, ageand gender-matched controls, SLE patients showed upregulation of MHC class II, with a mean expression of 130.5%736.8% (po0.007); CD86 in immature DC from SLE patients, generated in autologous human or control plasma, were also upregulated, with mean expression 106.6%718.0% (po0.03). A significant (420%) reduction in iC3b-apoptotic cell uptake, together with increased autologous mixed lymphocyte reaction, was seen in 75% of SLE patients. Mean 1,1 0 -dioctadecyl-3,3,3 0 ,3 0 -tetramethyl-indocarbocyanineperchloratestained apoptotic cell acquisition was 70.0%724% (po0.0001) compared with healthy controls. Altered generation of a tolerizing DC phenotype was seen in at least one third of SLE patients following interaction with iC3b-opsonized apoptotic cells. These results suggest that a substantial portion of SLE patients fail to generate DC with a tolerizing phenotype.

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Leucoytapheresis with Adacolumn® enhances HCV-specific proliferative responses in patients infected with hepatitis C virus genotype 1

Diepolder¹,

Kashiwagi²,

Teuber³

et al. 2005

J. Med. Virol.

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The most important aim in controlling virus infections is to destroy infected cells. Impaired cellular immunity in HIV and HCV infection leads to chronic infection. This study examined the effect of cytapheresis on the subsequent response to interferon/ribavirin treatment in patients infected with HCV. Adacolumn cytapheresis was carried out once a day for 5 consecutive days in patients who relapsed or did not respond to previous peginterferon and ribavirin combination treatment (n = 14: relapsers = 3, non-responders = 11). Peginterferon and ribavirin combination treatment was started after cytapheresis. During combination treatment, the proliferative response of peripheral blood mononuclear cells to HCV proteins (core, NS3, NS4, and NS5), tetanus toxoid, and phytohemagglutinin was measured, and compared to the early virological response. After treatment by leucocytapheresis, the proliferative response of peripheral blood mononuclear cells to HCV-core and tetanus toxoid increased significantly over the baseline (P < 0.05). A marked increase in the phytohemagglutinin response was observed after peginterferon and ribavirin combination treatment was started (P < 0.01 at week 5 and P < 0.005 at week 13). There were, however, no clear changes in the proliferative response to other antigens. Among the 14 patients, 12 (85.7%) achieved an early virological response by week 13 (12 weeks after the start of combination treatment). After treatment, nine patients (64.3%) had a significant proliferative response to HCV core antigen. Among the nine patients, eight patients (88.9%) achieved early virological response. The results indicate that activation of cellular immunity by leucocytapheresis facilitates an early virological response rate in HCV patients. This new therapy may, therefore, become an additional therapeutic measure for HCV.

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Phenotypic and functional deficiencies of monocyte-derived dendritic cells in systemic lupus erythematosus (SLE) patients

Cited by 47 publications

References 31 publications

Aberrant Phenotype and Function of Myeloid Dendritic Cells in Systemic Lupus Erythematosus

Aberrant Phenotype and Function of Myeloid Dendritic Cells in Systemic Lupus Erythematosus

Altered dendritic cells with tolerizing phenotype in patients with systemic lupus erythematosus

Leucoytapheresis with Adacolumn® enhances HCV-specific proliferative responses in patients infected with hepatitis C virus genotype 1

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