Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06126 (CD1a)
 2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cutaneous lymphocyte-associated antigen (CLA), recognized by the monoclonal antibody HECA-452, is a cell surface glycoprotein that binds specifically to E-selectin. CLA is present on most T cells at sites of cutaneous immune response and has been shown to be important in lymphocyte homing to the skin. It is expressed only by a minor subset of peripheral T cells and is absent on thymocytes. We have analysed (using a FACScan flow cytometer) the expression of CLA on human lymph cells derived from normal skin, from ultraviolet (UV)-irradiated skin and from allergic contact dermatitis. Whereas in the peripheral blood CLA was expressed on < 20% of CD4 +, CD8 + and CD56 + cells (natural killer cells), > 60% of CD4 +, CD8 + and CD56 + cells isolated from skin-derived lymph expressed CLA. Furthermore, > 90% of CD1a + dendritic lymph cells were positive for CLA. UV irradiation of the skin and induction of an allergic contact dermatitis did not change CLA expression on lymph cells, although lymph flow and cell output increased. These results provide further evidence for an important role of CLA in cell homing to the skin.
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PMID:The HECA-452 epitope is highly expressed on lymph cells derived from human skin. 1058 71

During differentiation of human monocytes (CD14(+)/CD1a(-)) to CD14(-)/CD1a(+)dendritic cells (DC), a drastic decrease in PDE4 activity was observed, while activities of PDE1 and PDE3 substantially increased. DC released tumour necrosis factor-alpha (TNF) in response to lipopolysaccharide (LPS) challenge, which was abolished both by dexamethasone and the cyclic AMP-elevating drugs db-cAMP and PGE(2). In addition, rolipram, at PDE4-selective concentrations, blocked TNF release by 37 +/- 5% (P<0.05 vs. control). The PDE3 inhibitor motapizone only marginally influenced TNF synthesis, but a synergistic inhibitory effect was noted in combination with rolipram. Qualitatively, similar inhibitory effects were observed in DC-stimulated T cell responses. Motapizone, lacking efficacy when used alone, increased the effect of rolipram in blocking CD4(+)T lymphocyte proliferation in response to antigen (Ag) (tetanus toxoid, TT; keyhole limpet hemocyanin, KLH) presented by DC and in allogeneic mixed leukocyte reactions (MLR). However, in these coculture systems the T cells rather than the DC seem to be the major target cells of PDE-inhibitor action. In summary, PDE inhibitors can affect DC function directly as demonstrated by blocking TNF release and their efficacy reflects the changes in the PDE activity profile during differentiation from their monocyte precursors. These results together with the known efficacy of PDE3/4 inhibitors in T cells support the concept of combined PDE3/4 inhibitors for asthma therapy.
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PMID:Characterization of the phosphodiesterase (PDE) pattern of in vitro-generated human dendritic cells (DC) and the influence of PDE inhibitors on DC function. 1058 79

Dendritic cells (DCs) are the most efficient antigen presenting cells (APCs) that initiate and modulate our internal immune responses in stimulating both B cells to produce various antibodies and T cells to control cell-mediated immunity. Such DCs can be classified into three groups based on their origin. One is the myeloid DCs originating from CD34+ stem cells that are further differentiated into CD14+ CD1a- phagocytotic, glass-adherent macrophages with the help of M-CSF, or into CD14- CD1a+, Birbeck granule containing LAG-1+ Langerhans cells by GM-CSF, TNF-alpha and TGF-beta 1 stimulation. The latter Langerhans cells appear to differentiate into DC1 as strong stimulators of T cells displaying large amounts of MHC-peptide complexes and co-stimulatory molecules, such as B7-1 and B7-2, after capturing antigens and migrating to a regional lymphoid organ. The second group is the lymphoid DCs originating from CD4+CD11c- cells, which differentiate into DC2 when cultured with IL-3. Third is the follicular dendritic cells (FDC) observed in lymphofollicules that capture foreign antigens with their Fc-receptor or complement-receptors and keep the antigens inside the follicules. DC1s secrete IL-12, which turns CD4 T cells into Th1 cells to induce cellular immunity, whereas DC2s favor production of Th2 cells to organize humoral immunity. Therefore, DCs appear to control our internal self-defense system. These unique features of DCs enable us to manipulate Th1 and Th2 activation selectively, and thus antigen-pulsed DCs are currently thought of as excellent tools to induce specific T cell immunity towards virus-infected cells or tumor cells.
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PMID:[Dendritic cells and tumor specific immunity]. 1063 93

Specimens from 17 head and neck tumor patients were immunohistochemically stained with monoclonal antibodies against HLA-DR, CD1a, RFD1, LAG, CD3, CD4, CD8, CD45RO, CD68, and cytokeratin to identify the nature and distribution of dendritic cells (DCs), T cells, and macrophages. Small numbers of DCs were present in all but 2 specimens. They were located between the tumor cells and in the stroma, especially in areas of inflammatory cell infiltration. Variable numbers of T lymphocytes (cytotoxic and memory type) occurred in the same locations. Numerous macrophages were found in the epithelium, in the stroma, and in the vicinity of tumor cells. The presence of DCs in head and neck tumors indicates that the organism has activated the immune surveillance system and is trying to present tumor antigens. Considering the sparsity of DCs in the malignant tissues, the T cell response can be only limited.
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PMID:Dendritic cells in selected head and neck tumors. 1065 14

This study shows that characteristic dendritic, antigen presenting cells, can be generated from adherent peripheral blood mononuclear cells (PBMC)/monocytes of uninfected and SIVsm-infected cynomolgus monkeys after stimulation in vitro with granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-4. The recruitment of monocyte derived dendritic cells (MDDC) was usually possible irrespective of the level of immunodeficiency (CD4-level) and viremia. The cynomolgus MDDC closely resembled their human counterpart (immature MDDC) with regard to capacity to upregulate CD1a, CD40, CD86 and human leukocyte antigen (HLA)-DR and develop dendrites and veiled processes. Such MDDC also increased their capacity for antigen uptake (dextran endocytoses/macropinocytosis) and for induction of T-cell proliferation in mixed leukocyte reaction (MLR) assays. However, although no clear difference with regard to phenotype and morphology was seen between MDDC from SIV-infected and uninfected monkeys, a reduction in MLR responsiveness in MDDC from SIV infected monkeys was consistently detected within each experiment.
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PMID:Recruitment of monocyte derived dendritic cells ex vivo from SIV infected and non-infected cynomolgus monkeys. 1065 63

Langerhans cells play an important role in the skin's immune system. Little is known, however, about the antigen-presenting capacity of Langerhans cells in the context of skin inflammation. By immunohistochemistry we investigated the phenotypic characteristics of epidermal and dermal Langerhans cells and their spatial relationship with infiltrating lymphocytes. We studied skin flaps autotransplanted to the oral cavity to fill a defect after maxillofacial cancer surgery. In 15 of 21 cases sampled for the present study, the skin flaps were severely inflamed by Candida albicans infection. In contrast to the normal skin, such inflamed skin showed a marked increase in CD1a(+) dermal Langerhans cells. Double immunohistochemistry revealed that dermal Langerhans cells abundantly expressed B7-2 (CD86), a representative costimulatory molecule, and CD83, a marker of mature dendritic cells. Furthermore, these dermal Langerhans cells were in close contact with CD4(+)/CD45RO(+) lymphocytes. This cell-to-cell contact was further visualized by immunoelectron microscopy. Langerhans cells were also observed within lymphatic vessels that were identified by the expression of vascular endothelial growth factor receptor-3. Ki-67 labeling indices were 4.2% in CD4(+) T cells and 0.8% in CD8(+) T cells within the dermis. Factor XIIIa(+) dermal dendrocytes were distributed outside the clusters of lymphocytes and were not in contact with them. Our observations indicate that dermal Langerhans cells in the inflamed skin are activated to express common phenotypes to mature dendritic cells so that they could stimulate neighboring memory CD4(+) T cells.
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PMID:Immunological activation of dermal Langerhans cells in contact with lymphocytes in a model of human inflamed skin. 1066 81

Dendritic cells (DCs) are powerful antigen-presenting cells. Because DCs are rare cells, methods to produce them in vitro are valuable ways to study their biologic properties and to generate cells for immunotherapy. This study defines the antigen-presenting properties of DCs generated in vitro from CD34+ cells of patients with breast cancer. The combination of cytokines flt3 ligand + c-kit ligand + granulocyte-macrophage colony-stimulating factor (GM-CSF) + interleukin-4 (IL-4) + tumor necrosis factor-alpha (TNF-alpha) was used to maximize the output of mature DCs in the culture of CD34+ cells while minimizing the production of monocytes. Cells grew and differentiated into DCs as measured by a time-dependent upregulation of cell surface antigens major histocompatibility complex class II, CD1a, CD80, CD86, CD40, and CD4, so that 40% +/- 9% (n = 6) of cells in culture at day 15 were CD1a+CD14-. Markers were acquired in the same sequence as on monocytes induced to differentiate with GM-CSF + IL-4. Differentiation was marked by a time-dependent increase in allostimulatory function, which, at its peak, was more potent than in cultures of DCs generated from monocytes with GM-CSF + IL-4, but was comparable on a cell-to-cell basis to that of mature monocytes cultured in flt3-ligand + c-kit-ligand + GM-CSF + IL-4 + TNF-alpha. Both CD34+ cell-derived and monocyte-derived DCs were able to process and to present tetanus toxoid and keyhole limpet hemocyanin to autologous T cells and to present major histocompatibility class I-binding peptides to CD8+ cytotoxic T lymphocytes inducing interferon-gamma production. Altogether, these results suggest that DCs generated from CD34+ cells of patients with breast cancer with flt3 ligand, c-kit ligand, GM-CSF, IL-4, and TNF-alpha are competent antigen-presenting cells, particularly for CD8+ cytotoxic T lymphocytes, and resemble mature monocyte-derived DCs in the assays described here.
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PMID:Dendritic cells generated from CD34+ progenitor cells with flt3 ligand, c-kit ligand, GM-CSF, IL-4, and TNF-alpha are functional antigen-presenting cells resembling mature monocyte-derived dendritic cells. 1068 37

A double blind left, right comparative study was carried out in 17 psoriatic subjects to examine the influence of a topically applied inhibitor of nitric oxide (NO) synthesis on the pathogenic events of psoriasis. The inhibitor NG-monomethyl-L-arginine (L-NMMA) in aqueous cream BP was applied to one plaque while aqueous cream BP alone served as control. Compared with the control, the L-NMMA-treated side showed significant (77%) inhibition of NO production and a reduction in blood flow, confirming its bioavailability. L-NMMA significantly reduced staining for endothelial cells and intercellular adhesion molecule 1, while CD1a-positive Langerhans cells and CD8-positive suppressor cytotoxic T cells increased. CD4-positive lymphocytes and epidermal proliferation, as indicated by Ki-67 staining, were unaffected by this degree of inhibition of NO synthesis, and correspondingly significant clinical improvement was not found.
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PMID:Treatment of psoriasis with topical NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthesis. 1080 60

Dendritic cell (DC) precursors and immature DC reside in epithelium where they encounter pathogens and cytokines, which stimulate their differentiation. We hypothesized that type-I interferons (IFN-alpha and -beta), cytokines that are produced early in the innate immune response against viruses and some bacteria, may influence DC differentiation and function. To examine this possibility, we used an in vitro model of DC differentiation in which initial culture of human CD14(+) monocytes with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 generates immature DC, and subsequent culture with tumor necrosis factor (TNF)-alpha drives the final development into mature DC. We found in this model that IFN-alpha/beta, added from the initiation of the culture on, significantly reduced the survival and altered the morphology and differentiation of DC. TNF-alpha-dependent maturation of IFN-beta-treated immature DC led to cells with reduced expression of CD1a, CD40, CD54, and CD80 when compared with mature DC controls. IFN-alpha/beta-treated DC further had a reduced capacity to induce naive Th-cell proliferation through allostimulation or anti-CD3 monoclonal antibody stimulation. In addition, IFN-alpha/beta-treated DC secreted less IL-12 upon stimulation with Staphylococcus aureus Cowan strain or with CD4(+) T cells, and this decrease correlated directly with their inability to support CD4(+) T-cell secretion of IFN-gamma, even though T-cell lymphotoxin production was unaffected. These findings indicate that type-I IFNs can influence the generation of acquired immune responses by modifying T-helper cell differentiation through the regulation of DC differentiation and function.
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PMID:Interferon-alpha and -beta inhibit the in vitro differentiation of immunocompetent human dendritic cells from CD14(+) precursors. 1089 53

In normal T-cell development, IL-7 plays a nonredundant role as an antiapoptic factor by regulating Bcl-2 expression in pro-T cells. In the current study, we addressed the roles of IL-7 and related cytokines as apoptosis-modulating factors in precursor T-cell acute lymphoblastic leukemia (T-ALL). To this end, leukemic blasts from pediatric patients with T-ALL were prospectively investigated as to their responsiveness to IL-7, IL-4, and IL-2 (in terms of modulation of spontaneous apoptosis, assessed by flow cytometry), cytokine receptor expression profiles, and expression levels of Bcl-2 and Bax proteins. IL-7, in contrast to IL-4 and IL-2, was highly efficient in apoptosis inhibition, and this effect correlated with the expression levels of IL-7Ralpha chain and with the up-regulation of Bcl-2 protein expression (P <.0001). Subclassification of T-ALL samples (n = 130) according to their in vitro IL-7 responses revealed that IL-7 refractory samples were more frequently positive for CD34 (P <.0001) and the myeloid-associated antigen CD33 (P =.01), whereas IL-7 responsiveness was associated with an expression of more mature differentiation-associated T-cell antigens (CD1a, surface CD3, CD4/8; P <.05). Furthermore, the extent of apoptosis inhibition by IL-7 in vitro quantitatively correlated with early cytoreduction as determined by the prednisone peripheral blood response on day 8 and cytoreduction in the marrow on day 15 (n = 87; P <.05). Multivariate analysis of the apoptosis-related parameters investigated, including spontaneous apoptosis, its inhibition by IL-7, and expression levels of Bcl-2 and Bax, showed that only IL-7 responsiveness has an independent impact on early cytoreduction (P <. 05), thus indicating a potential prognostic relevance of IL-7 sensitivity in T-ALL.
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PMID:Inhibition of in vitro spontaneous apoptosis by IL-7 correlates with bcl-2 up-regulation, cortical/mature immunophenotype, and better early cytoreduction of childhood T-cell acute lymphoblastic leukemia. 1089 65


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