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Results for “CD83 Antigen”

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PubMed1997

Hodgkin's cells express CD83, a dendritic cell lineage associated antigen.

Hodgkin's cells (HC) are considered to be the malignant cells of Hodgkin's disease (HD), but despite extensive studies, no conclusive evidence has emerged regarding their non-malignant counterpart and the ontogeny of these cells remains controversial. The analysis of a possible dendritic cell (DC) origin of HC has been hampered to date by the lack of a DC lineage specific marker. The expression of the two DC-associated antigens CD83 and CMRF-44, the B lymphocyte restricted molecule CD79, and the costimulator molecule CD86, was examined in lymph nodes from 23 HD patients using immunohistological techniques. The majority of HC expressed the CD83 (22/23) and CD86 antigens (20/23), whereas expression of the CMRF-44 antigen was variable (10/23) and usually only a subpopulation of HC stained. In contrast, the CD79 antigen was absent from most HC (17/23). The presence of the CD83 antigen on HC in the absence of the CD79 antigen supports a possible DC lineage origin for some HC. Regardless of its role in lineage assignment, CD83 may become a useful immunohistological marker for HD as the CD83 antigen was present on most HC.

Antibodies, Monoclonal↗

PubMed1997

Bacillus Calmette-Guérin mycobacteria stimulate human blood dendritic cells.

Bacillus Calmette-Guérin (BCG) mycobacteria have been used as adjuvant in the active immunotherapy of various human cancers. In addition, dendritic cells, which are the most potent antigen-presenting cells, have been shown to be capable of initiating anti-tumor immune responses. Here we investigated the effects of BCG on dendritic cells cultured from human blood. Addition of BCG resulted in rapid homotypic adhesion of dendritic cells. Moreover, BCG concentrations ranging from 10(4) to 10(6) bacteria/ml enhanced expression of the dendritic-cell-maturation antigen CD83 and of the T-cell co-stimulator CD86 (B7-2) in a dose-dependent manner. Concomitant with the increase of CD83 and CD86 expression, the cells lost the ability to capture soluble antigens, as determined by the exclusion of fluoresceinated Dextran molecules. Strikingly, the same dosages of BCG-bacteria stimulated TNF-alpha-gene transcription and TNF-alpha-protein release from dendritic cells in a dose-dependent fashion. BCG infection of dendritic cells in the presence of a neutralizing antibody directed against TNF-alpha inhibited CD83 expression by more than 50% indicating that the BCG-induced maturation of dendritic cells was at least partially mediated by dendritic-cell-derived TNF-alpha. The finding that BCG activates the most potent antigen-presenting cells reveals a plausible immunological mechanism of the occasionally observed anti-tumor activity of BCG.

Antibodies, Monoclonal↗

PubMed2003

A protocol for generation of clinical grade mRNA-transfected monocyte-derived dendritic cells for cancer vaccines.

With the aim of producing large quantities of mRNA-transfected monocyte-derived dendritic cells (DCs) to be used as cancer vaccines, a new clinical grade procedure has been developed. Peripheral blood mononuclear cells (PBMCs) obtained by leukapheresis were enriched for monocytes by immunomagnetic depletion of CD19+ B cells and CD2+ T cells employing the ISOLEX 300i device. After 5 days of culture of enriched monocytes in gas permeable Teflon bags, using serum-free medium supplemented with granulocyte/macrophage-colony stimulating factor and interleukin-4 (IL-4), immature DCs were generated. Following transfection with mRNA from three human prostate cancer cell lines (DU145, LNCaP and PC-3), employing a newly developed square wave electroporation procedure, the immature DCs were immediately transferred to Teflon bags and matured for 48 h, using serum-free medium supplemented with IL-1alpha, IL-6, tumour necrosis factor-alpha and PGE2. The electroporation procedure efficiently transferred mRNA into the DCs with minor effect on the viability of the cells. The generated matured transfected DCs show high expression of the antigens CD83, CD80, CD86 and human leucocyte antigen-DR. Freezing and thawing of the transfected matured DCs had minor effect on cell viability and the phenotype. From 4 x 109 PBMCs, about 1 x 108 transfected matured DCs are produced. The thawed transfected DCs were able to elicit primary T-cell responses in vitro against antigens encoded by the prostate cancer mRNA as shown by enzyme-linked immunospot assay using mock-transfected DCs as control. Based on these results, clinical trials in cancer patients have been initiated.

Adult↗

PubMed2001

Characterization of antigen-presenting dendritic cells in the peripheral blood and colonic mucosa of patients with ulcerative colitis.

OBJECTIVE: Increased lymphocyte activation and production of inflammatory cytokines are implicated in the pathogenesis of ulcerative colitis. Because antigen-presenting dendritic cells play a cardinal role in the activation and survival of activated lymphocytes, the aim of the present study was to characterize dendritic cells in ulcerative colitis. DESIGN: This study was designed to compare the phenotypes and functions of peripheral blood dendritic cells among healthy normal volunteers and patients with ulcerative colitis or Crohn's disease. Activated dendritic cells were also localized at the colonic mucosa. METHODS: Peripheral blood dendritic cells were generated from 15 patients with ulcerative colitis, 10 patients with Crohn's disease and 15 healthy control volunteers. The stimulatory capacities of dendritic cells were analysed in an allogenic mixed lymphocyte reaction. Nitric oxide was detected by the Griess method. Single- and dual-colour flow cytometry was employed to study the levels of maturation of dendritic cells. Activated dendritic cells were localized immunohistochemically in the colonic mucosa. RESULTS: In comparison to normal controls, peripheral blood dendritic cells from patients with ulcerative colitis showed significantly increased stimulatory capacities (P < 0.05) and produced significantly higher levels of nitric oxide (P < 0.05). The numbers of activated dendritic cells were also significantly higher in ulcerative colitis (P < 0.05). Mature and activated dendritic cells expressing the CD83 antigen were detected at the inflamed colonic mucosa in patients with ulcerative colitis and Crohn's disease. CONCLUSIONS: Activated and mature dendritic cells may have a role in the induction of an exacerbated immune response in ulcerative colitis. This study provides the scientific and logical basis for blocking the maturation and activation of dendritic cells in ulcerative colitis as a new therapeutic intervention.

Adult↗

PubMed1996

Human renal-cell carcinoma tissue contains dendritic cells.

Immune surveillance of cancer requires antigen-presenting cells which activate T cells specific for tumor-associated antigens. We show here that substantial numbers of dendritic cells, which are the most potent antigen-presenting cells, emigrate from renal-tumor explants in organ culture. Tumor-derived dendritic cells presented with all characteristics of mature dendritic cells. Dendritic cells could be identified by typical cytoplasmic projections (=veils). They expressed high levels of MHC products and of the co-stimulator CD86 (B7-2). Dendritic cells expressed the CD45RO isoform but not CD45RA. The most important point was that up to 9% of the emigrating leukocytes expressed the CD83 antigen, a specific marker for mature dendritic cells. CD83+ cells were approximately 40-fold enriched in the tumor tissue as compared to the peripheral blood. In contrast to cultured blood dendritic cells, tumor-emigrant dendritic cells had a reduced potential to capture soluble antigen, as shown by the exclusion of fluoresceinated Dextran molecules. Finally, in mixed leukocyte reactions, tumor-derived dendritic cells were able to stimulate naive T cells from cord blood, which is a unique feature of dendritic cells. This study demonstrates that genuine dendritic cells reside in or infiltrate renal-cell carcinoma tissue. The failure of patients with renal-cell carcinoma to mount an anti-tumor immune response despite the presence of professional antigen-presenting cells in the tumor tissue suggests that tumor-associated dendritic cells are suppressed in situ, in a similar way to that described for tumor-infiltrating lymphocytes.

Antigens, CD↗

PubMed2005

Impaired accessory cell function in a human dendritic cell line after human immunodeficiency virus infection.

We generated human dendritic cell (DC) hybridoma cell lines by fusing HGPRT-deficient promonocytic U937 cells with immature DCs obtained by culturing peripheral blood monocytes with interleukin-4 (IL-4; 1,000 U/ml) and granulocyte-macrophage colony-stimulating factor (100 U/ml) for 7 days and mature DCs by treatment with tumor necrosis factor alpha (12.5 microg/ml) for 3 days. Only one fusion with immature DCs was successful and yielded four cell lines--HB-1, HB-2, HB-3, and HB-9--with an overall fusion efficiency of 0.0015%. The cell lines were stable in long-term culture, displayed morphological features typical of DCs, and expressed distinct class I and class II molecules not present on U937 (A*031012, B*51011, Cw*0701, DRB3*01011 52, and DR5*01011). A representative cell line, HB-2, that expressed DC markers including CD83, CD80 and CD86 could be induced to produce IL-12 through CD40 stimulation. After human immunodeficiency virus (HIV) infection, there was impairment of antigen-presenting cell (APC) function, which was manifested by an inability to stimulate allogeneic T-cell responses. There was no change in expression of major histocompatibility complex class I and class II antigens, CD83, CD40, CD4, CD11c, CD80, CD86, CD54, and CD58, or IL-12 production in the HIV-infected HB-2 cells. The HIV-infected HB-2 cells induced T-cell apoptosis in the cocultures. T-cell proliferation could be partially restored by using ddI, indinivir, and blocking anti-gp120 and anti-IL-10 antibodies. Our data suggest that there are multiple mechanisms that DCs use to inhibit T-cell responses in HIV-infected patients. The HB-2 cell line could be a useful model system to study APC function in HIV-infected DCs.

Antigen Presentation↗

PubMed1997

Prostaglandin E2 and tumor necrosis factor alpha cooperate to activate human dendritic cells: synergistic activation of interleukin 12 production.

Interleukin (IL)-12 is a proinflammatory cytokine that contributes to innate resistance and to the development of antigen-specific T cell responses. Among other effects, prostaglandin E2 (PGE2) inhibits the production of IL-12 by macrophages activated with lipopolysaccharide (LPS). Here we investigated the effects of PGE2 on human dendritic cells (DCs) which develop in the presence of GM-CSF and IL-4. We demonstrate that in the absence of LPS, PGE2 dose dependently stimulated the production of IL-12 by DCs. Although PGE2 alone stimulated the production of low amounts of IL-12 only, it synergized with tumor necrosis factor (TNF)-alpha to induce high levels of IL-12 production by DCs. Addition of TNF-alpha in the absence of PGE2 had no effect on IL-12 production. Conversely, in the presence of LPS, PGE2 inhibited IL-12 production by DCs in a dose-dependent manner. The combination of PGE2 and TNF-alpha efficiently silenced mannose receptor-mediated endocytosis in DCs and readily induced neo-expression of the CD83 antigen. In addition, the expression of various surface antigens such as major histocompatibility complex class I and II, adhesion, as well as costimulatory molecules was upregulated by this treatment. The effects of PGE2 on IL-12 synthesis and CD83 expression could be mimicked by dibutyryl-cAMP and forskolin, indicating that they were due to the intracellular elevation of cAMP levels. DC treated with PGE2 and TNF-alpha were most potent in stimulating allogeneic T cell proliferation. Our data demonstrate that PGE2 contributes to the maturation of human DCs and that PGE2 can be a potent enhancer of IL-12 production by human DCs.

Antigen Presentation↗

PubMed2004

Opsonization with a trifunctional bispecific (alphaCD3 x alphaEpCAM) antibody results in efficient lysis in vitro and in vivo of EpCAM positive tumor cells by cytotoxic T lymphocytes.

Removab is a trifunctional bispecific antibody which can bridge CD3+ T cells and epithelial cell adhesion molecule positive (EpCAM+) tumor cells, and binds with its Fc fragment to antigen presenting cells. To explore a new approach for the treatment of patients with carcinoma of the upper aerodigestive tract, we investigated whether Removab can induce specific cellular responses to the EpCAM+ carcinoma cell line BHY. Particular emphasis was put on the opsonization of peripheral blood mononuclear cells (PBMN) with respect to clinical application. Tumor cells and allogeneic PBMN of healthy volunteers were incubated with or without Removab. In a third group, PBMN were opsonized with Removab and washed before incubation with tumor cells. Inverse microscopy, ELISPOT, flow cytometry analysis and cytotoxicity assays on the chorioallantois membrane (CAM) were performed. In comparison with PBMN alone, opsonization with Removab resulted in: a) activation of CD83+ antigen presenting cells, b) secretion of interferon gamma, and c) granzyme B mediated lysis of targeted BHY cells by EpCAM specific CD8+ T cells. The secretion of tumor necrosis factor alpha, interferon gamma and interleukin-2 by opsonized PBMN was significantly reduced after 24 h. Washed opsonized PBMN maintained their lytic activity against tumor cells as tested on the CAM. Removab is an appropriate agent for the therapeutic amplification of T cell responses against EpCAM+ tumor cells by opsonization of PBMN without putting patients at risk for severe adverse events caused by a cytokine storm.

Antibodies, Bispecific↗

PubMed2005

[Immunotherapy for leukemia cells by using cytotoxic T lymphocyte specifically against WT1-derived peptide: an experimental study in vitro].

OBJECTIVE: To investigate the effect of targeting immunotherapy for leukemia cells by using cytotoxic T lymphocyte (CTL) specifically against WT (Wilm's tumor) 1-derived peptide. METHODS: A 9-mer WT1 peptide (CMTWNQMNL) containing HLA-A*0201-binding anchor motifs was synthesized. Dendritic cells (DCs) generated from the peripheral blood mononuclear cells of an HLA-A*0201-positive healthy donor were cultured and divided into 2 groups: experimental group to be loaded with Wilms' tumor 1 (WT1) peptide so as to elicit CTL's specifically for WT1 peptide, restricted by HLA-A*0201, and control group. Six days later rhTNF-alpha was added for 3 days more to promote the maturation of DCs. Before loading of WT1 peptide and 2 days after the addition of rhTNF-alpha direct immunofluorescence labeling method was used with PE or FITC labeled mono-antibodies to detect the expression of the surface antigens: CD83, CD1alpha, CD80, CD86, CD14, and HLA-DR. DCs suspended and attached to wall were collected and then divided into 2 groups: pure T cell group (group D) to be cultured in culture medium without IL-2, and IL-2 + T cell group (Group C) to be cultured in 1640 culture medium with IL-2. Eight days later the T cells of Group C were co-cultured with the DCs of the experimental group (WTI peptide + DC + IL-2 + T cells, Group A) or the DCs of the control group (DC + IL-2 + T cells, Group B). Five days later the killing activity was detected. The CTLs of Groups A, B, and C at logarithmic growth phase were mixed with leukemic cells of the lines: NB4/WT1D, NB4WT1A, NB4 (all HLA-A*0201 +, WT1 +), U937 (HLA-A*0201 +, WTl -), and K562 (HLA-A*0201 -, WTI +), and mononuclear cells of the bone marrow of leukemic patients at different effector cell-target cell of 20:1 and 10:1. MTT method was used to examine the killing rate of CTL to the target cells. RESULTS: (1) The killing rates of Group A cells to NB4/WT1 D, NB4WTA, and NB4, leukemic cells were 60.4% +/- 3.1%, 56.4% +/- 5.7%, and 55.0% +/- 3.7%, all significantly higher than those of the Group B cells (10.9% +/- 1.6%, 11.1% +/- 2.7%, and 11.9% +/- 2.5%), and those of Group C cells (9.1% +/- 1.0%, 9.2% +/- 1.7%, and 9.4% +/- 1.8%) (all P < 0.01). There were no significant differences in the killing rates to U937 and K562 leukemic cells among the 3 groups. (2) When the effect-target ratio was 20: 2, the killing activity of the CTLs of Group A to the HLA-A*0201 +, WT1 + NB4/WT1 D, NB4/WT1A and NB4 leukemic cells was significantly higher than those to the HLA-A*0201 +, WT1 - U937 cells and the HLA-A*0201 -, WT1 + K562 cells (both P < 0.001), however, not significantly different from that to the U937 and K562 cells. (3) There were no significant differences in the killing activity of Group A cells to NB4/WT1D, NB4/WT1A, and NB4 cells (P = 0. 065, P = 0.621). (4) When the effect-target ratio was 10:2, the killing rates of Group A cells to the NB4/ WT1D, NB4/WT1A, and NB4 cells were 45.9% +/- 3.9%, 43.9% +/- 3.7%, and 44.1% +/- 3.2% respectively, all significantly lower than those when the effect-target ratio was 20:1 (all P < 0.01). CONCLUSION: CTLs specific for WT1 and restricted by HLA-A*0201 exert specific lysis upon leukemia cell lines and primary leukemia cells, but not upon normal hematopoietic cells, which provides a rationale for developing a strategy of WT1 peptide-based adoptive T-cell therapy and vaccination for human leukemia and solid tumors.

Amino Acid Sequence↗

PubMed1999

Dendritic cells in chronic myelomonocytic leukaemia.

Blood dendritic cells (DC) differentiate in vitro via two separate pathways: either directly from blood DC precursors (DCp) or from CD14+ monocytes. In chronic myelomonocytic leukaemia (CMML) abnormal bone marrow precursors contribute to blood monocyte development but DC development has not been studied previously. Monocytes comprised 60% of blood MNC in 15 CMML patients studied, compared with 20% in 16 age-matched controls. The increase in blood monocytes was accompanied by a reciprocal decrease in mean blood DC percentage (from 0.42% of MNC in normal individuals to 0.16% of MNC in CMML patients). Absolute blood DC numbers showed a minimal (non-significant) reduction from 9.8 x 10(6)/l in normal individuals to 7.5 x 10(6)/l in CMML patients. The CD14(low) WCD16+ monocyte subpopulation was not found in CMML patients. After culture in GM-CSF/IL-4, CMML CD14+ monocytes acquired the phenotype of immature monocyte derived DC (Mo-DC) with similar yields to normal blood Mo-DC generation. Addition of TNF-alpha or LPS induced both normal and CMML Mo-DC to express prominent dendritic processes, the CMRF44+ and CD83+ antigens and high levels of HLA-DR, CD80 and CD86. Treatment either with TNF-alpha or LPS increased the allostimulatory activity of normal Mo-DC, but had little effect on the allostimulatory activity of CMML Mo-DC, perhaps reflecting the underlying neoplastic changes in monocyte precursors. We conclude that the blood DC numbers are relatively unaffected in CMML, suggesting discrete regulation of monocyte and DC production.

Adult↗

PubMedDate not supplied

Presentation of tumor antigens by dendritic cells genetically modified with viral and nonviral vectors.

Genetic modification of dendritic cells (DCs) with recombinant vectors encoding tumor antigens may aid in developing new immunotherapeutic treatments for patients with cancer. Here, we characterized antigen presentation by human DCs genetically modified with plasmid cDNAs, RNAs, adenoviruses, or retroviruses, encoding the melanoma antigen gp100 or the tumor-testis antigen NY-ESO-1. Monocyte-derived DCs were electroporated with cDNAs or RNAs, or transduced with adenoviruses. CD34+ hematopoietic stem cell-derived DCs were used for retroviral transduction. Genetically modified DCs were coincubated with CD8+ and CD4+ T cells that recognized major histocompatibility complex class I- and class II-restricted epitopes from gp100 and NY-ESO-1, and specific recognition was evaluated by interferongamma secretion. Cytokine release by both CD8+ and CD4+ T cells was consistently higher in response to DCs modified with adenoviruses than cDNAs or RNAs, and maturation of DCs after genetic modification did not consistently alter patterns of recognition. Also, retrovirally transduced DCs encoding gp100 were well recognized by both CD8+ and CD4+ T cells. These data suggest that DCs transduced with viral vectors may be more efficient than DCs transfected with cDNAs or RNAs for the induction of tumor reactive CD8+ and CD4+ T cells in vitro and in human vaccination trials.

Adenoviridae↗

PubMed2003

The circulating dendritic cell compartment in patients with chronic lymphocytic leukemia is severely defective and unable to stimulate an effective T-cell response.

Chronic lymphocytic leukemia (CLL), the most frequent leukemia in the Western world, is characterized by a profound dysregulation of the host immune system that has a marked impact on the clinical course of the disease. To date, the competence of the circulating dendritic cell (DC) compartment in CLL patients has not been investigated. To address this issue, we sorted DC precursors from the peripheral blood of CLL patients and found a profoundly altered compartment as compared with normal donors. CLL DCs proved a morphologically and phenotypically immature population, lacking the maturation antigen CD83 and the costimulatory molecule CD80, unable to induce a significant proliferative response in allo-mixed lymphocyte reaction, with a reduced ability to release interleukin 12 and to drive a type 1 T-cell response. To investigate whether these defects could be ascribed to inhibiting soluble factors released by the leukemic clone, DCs were generated in vitro from normal monocytes in the presence of allogeneic CLL cells. The addition of CLL cells induced similar markers of abnormal maturation and functional impairment with an inhibition in the expression of costimulatory molecules and a reduction of their allo-stimulatory ability. The blocking of interleukin 6 activity was able to revert the inhibition in a proportion of patients. Taken together, these findings indicate that mechanisms of tumor-induced DC inhibition are operational in CLL patients, resulting in both maturative and functional defects in the circulating DC compartment, with a potential functional impact in the regulation of in vivo T-cell immune responses.

Dendritic Cells↗

PubMed1996

Chimpanzee dendritic cells with potent immunostimulatory function can be propagated from peripheral blood.

We have established dendritic cell (DC) cultures from chimpanzee peripheral blood mononuclear cells (PBMC) by using recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) and rh interleukin-4 (IL-4) and demonstrate that these cells have all the characteristics of DC as described for other species. We consistently can obtain 1 x 10(7) DC per 100 ml of blood, a yield of 5% DC as compared to 0.1 to 0.5% DC reported in fresh human PBMC. The cultured DC have a varied morphology with typical cytoplasmic extensions. Phenotypically, the blood-derived DC lack expression of most lineage antigens, but express CD83, an antigen specifically expressed on human blood DC. Chimpanzee DC express very high levels of major histocompatability complex class II antigens, adhesion and costimulatory molecules. Consistent with this phenotype of a powerful antigen-presenting cell, chimpanzee DC generate allogeneic mixed leukocyte responses 15 to 20 times more potent than that elicited by macrophages, Epstein-Barr virus-transformed lymphoblasts and fresh PBMC. In addition, chimpanzee DC very efficiently present tetanus toxoid to PBMC-derived CD4+ T cells as compared to macrophages and PBMC. The DC generated by culturing chimpanzee PBMC with rhGM-CSF and rhIL-4 thus closely resemble human blood-derived DC propagated in the same manner. This technology provides a powerful animal model with which to apply DC to clinical studies with relevance to human disease. In particular, chimpanzee DC can be tested as immunotherapeutic agents for cancer, and be studied in relation to the pathogenesis of human immunodeficiency virus (HIV) infection.

Animals↗

PubMed2002

Native and genetically inactivated pertussis toxins induce human dendritic cell maturation and synergize with lipopolysaccharide in promoting T helper type 1 responses.

The capacity of pertussis toxin (PT) to induce maturation and functional activities of human monocyte-derived dendritic cells (DCs) was investigated. Both native PT (nPT) and genetically detoxified PT (dPT) efficiently promoted expression on DCs of CD80, CD86, human leukocyte antigen-DR, and CD83 markers, alloreactive antigen presentation, and cytokine production, primarily interferon (IFN)-gamma. Although they did not affect interleukin (IL)-10 production by lipopolysaccharide (LPS)-stimulated DCs, both nPT and dPT strongly synergized with LPS for IL-12 production. PTs plus LPS-stimulated DCs secreted soluble factors fostering IFN-gamma but not IL-4 and IL-5 production by naive T cells. T helper type 1 (Th1) polarization was, as alloreactive antigen presentation, inhibited by anti-IL-12 monoclonal antibody. These findings support the notion that nPT, in addition to inducing specific immune response, is a potent Th1 adjuvant and that dPT fully preserves this adjuvanticity. The synergic interaction between PT and LPS in IL-12 production might be relevant for the mechanisms of vaccine-induced protection.

Antigens, CD↗

PubMed2004

CD38 is expressed on human mature monocyte-derived dendritic cells and is functionally involved in CD83 expression and IL-12 induction.

Dendritic cell (DC) maturation is characterized by the gain or loss of immunological functions and by expression of distinctive surface receptors. CD38 is an ectoenzyme that catalyzes the synthesis of cyclic ADP ribose (a potent second messenger for Ca(2+) release), as well as a receptor that initiates transmembrane signaling upon engagement with its counter-receptor CD31 or with agonistic monoclonal antibodies. Since CD38 is expressed by resting monocytes, we aimed to monitor CD38 expression during the differentiation of human monocyte-derived DC (MDDC) and to investigate the possibility that CD38 plays a functional role during DC maturation. CD38 is down-modulated during differentiation into immature MDDC and expressed again upon maturation. The extent of CD38 expression is dependent on the stimulus adopted (LPS > IFN-gamma > CD40 cross-linking). Although weak, IFN-gamma consistently induces DC maturation. De novo-synthesized CD38 is enzymatically active, and its expression in mature (m) MDDC is dependent on NF-kappa B activity. However, CD38 is not merely a maturation marker but also mediates signaling in mMDDC, where it maintains its functions as a receptor. Activation via agonistic anti-CD38 mAb induces up-regulation of CD83 expression and IL-12 secretion, whereas disruption of CD38/CD31 interaction inhibits CD83 expression, IL-12 secretion and MDDC-induced allogeneic T cell proliferation.

ADP-ribosyl Cyclase↗

PubMed2002

In situ localization of CD83-positive dendritic cells in psoriatic lesions.

BACKGROUND: Dendritic cells (DC) are considered to be the most potent antigen-presenting cells, and CD83 is expressed at a high level on immune-competent, activated and mature DC. Although changes in the number or localization of mature and activated CD83+ DC could be expected in psoriasis, there is little information on such changes. AIM: Morphological identification of CD83+ DC in psoriatic skin lesions. MATERIALS AND METHODS: Immunohistochemical staining was performed in 5 specimens of psoriasis vulgaris and 6 specimens of pustular psoriasis. Formalin-fixed, paraffin-embedded sections were used for examination in this study. The skin sections were pretreated with 0.1% trypsin for 60 min at 37 degrees C prior to immunostaining for CD83. RESULTS: A small but significant subpopulation of CD83+ DC was found in the upper dermis. In addition, CD83+ DC were occasionally scattered in the epidermis. The most common distribution pattern of CD83+ DC was as clusters with mononuclear lymphoid cells in the upper dermis. CD83+ DC were in close contact with lymphocytes. High-intensity staining of CD83 antigens was detected not only on the surface, but also in the cytoplasm of DC. CONCLUSION: These results indicate that activated and mature CD83+ DC may play a role in the immune response in psoriasis and provide in vivo support for the concept that CD83+ DC provide signals for direct intralesional T cell activation.

Antigens, CD↗

PubMed1998

Dermal dendritic cells associated with T lymphocytes in normal human skin display an activated phenotype.

The CMRF-44 and CD83 (HB15) antigens are associated with functional maturation and activation of blood dendritic cells (DC). We describe the expression of these antigens on freshly isolated epidermal Langerhans cells and dermal DC as well as the distribution of CD83+/ CMRF-44++-activated DC within sections of normal human skin. Fresh Langerhans cells were prepared by standard techniques and large numbers of enriched (25%-55%), viable dermal DC were obtained using an improved collagenase treatment protocol with density gradient enrichment. Freshly isolated Langerhans cells and dermal DC had similar costimulator and activation antigen expression, and both stimulated moderate levels of allogeneic T lymphocyte proliferation as determined in the 7 d mixed leukocyte reaction. In situ labeling of DC within skin sections revealed a population of CD83 and CMRF-44 positive dermal cells of which most (approximately 75%) were in intimate contact with CD3+ T lymphocytes, especially in the adnexal regions. In contrast, only 25%-30% of the more numerous CD1a++ dermal DC population were directly apposed to T lymphocytes. The CMRF-44++ dermal DC population stimulated an allogeneic mixed leukocyte reaction, confirming their identity as DC. These data, plus comparative data obtained for migratory dermal DC, suggest that only a small proportion of dermal DC have been triggered to a more advanced state of differentiation or activation. The striking association of the activated dermal DC population with T lymphocytes suggests that communication between these two cell types in situ may occur early in the immune response to cutaneous antigen.

Antigen-Presenting Cells↗

PubMed2003

Activated and mature CD83-positive dendritic cells and interferon-gamma-positive cells in skin eruptions of secondary syphilis.

Dendritic cells are considered to be the most potent antigen-presenting cells, and CD83 is expressed at a high level in immunocompetent, activated and mature dendritic cells. Various pathogens can activate and modulate the function of dendritic cells. The presence of activated and mature dendritic cells in skin lesions of secondary syphilis has never been reported. In the present study, an immunohistochemical technique was used to determine the exact tissue distributions of CD83+ dendritic cells and interferon-gamma+ cells in skin lesions of patients with secondary syphilis. Immunohistochemical staining was performed by using formalin-fixed, paraffin-embedded sections. A small but significant subpopulation of CD83+ dendritic cells was found in the dermis. CD83+ dendritic cells were in close contact with lymphocytes. High-intensity staining of CD83 antigens was detected not only on the surface but also in the cytoplasm of dendritic cells. Infiltrating mononuclear cells were stained positively for CD4 or CD8, with CD8+ cells always being in the majority. A small number of interferon-gamma+ cells resembling mononuclear lymphoid cells were detected in all samples. These results provide in vivo support for the hypothesis that dendritic cells are activated by Treponema pallidum and that thus activated and mature CD83+ dendritic cells may play a role in the Th1 response in secondary syphilis.

Antigens, CD↗