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

Morphology, phenotype, and enzyme activity of highly enriched (80%) unlabeled human epidermal Langerhans cells (LC) have been studied, with emphasis on changes during a short-term culture of three days in vitro. All freshly isolated LC contained Birbeck granules and expressed high levels of CD1a, CD1c, and MHC class II molecules HLA-DR, -DP, and -DQ. They have a weak to moderate expression of RFD1, C3biR, Fc gamma R, p 150/95, MHC class I molecules HLA-ABC, and of the adhesion molecules LFA-3 and ICAM-1, whereas no expression of LFA-1 and several monocyte/macrophage markers were detected. Human LC undergo profound changes during in vitro culture. Birbeck granules, C3biR, Fc gamma R, and p 150/95 were completely lost and the expression of CD1a and CD1c was markedly decreased or lost. Expression of molecules that have essential functions in antigen presentation remained present at the same level (MHC class II molecules and ICAM-1) or was markedly enhanced (LFA-3 and MHC class I). Highly remarkable was the dramatically enhanced expression of interdigitating cell marker RFD1. The monocyte/macrophage markers initially absent remained absent and the enzyme activity initially present (including ATPase and nonspecific esterase) remained present. In conclusion, the results in this report stress rapid alterations of human LC during in vitro culture, resulting in transformation into cells that have phenotypical characteristics of potent antigen presenting cells that resemble interdigitating cells.
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PMID:Human epidermal Langerhans cells undergo profound morphologic and phenotypical changes during in vitro culture. 240 65

Expression of adhesion molecules was investigated in six biopsy specimens of Langerhans' cell histiocytosis using immunocytochemistry. Cells with Langerhans' cell histiocytosis morphology were stained for ICAM-1, for the beta-1 integrins alpha-4 (VLA-4) and alpha-5 (VLA-5) , and for the beta-2 integrins LFA-1, MAC-1 and p150,95. This pattern of reactivity was different from that of epidermal Langerhans' cells of the normal skin which were not immunostained. A variable number of CD68+ multinucleated giant cells was present in five biopsies. They were less reactive than the cells of Langerhans' cell histiocytosis for alpha-4 (VLA-4) and LFA-1, were positive for MAC-1 and p150,95 and were characterized by prominent expression of the beta-1 integrins alpha-2 (VLA-2), alpha-3 (VLA-3) and of VnR (alpha-v/beta-3). The repertoire of adhesion molecules expressed by giant cells is indicative of profound cell-matrix interactions, whereas that of Langerhans' histiocytosis cells suggests particularly active cell-cell interactions. Blood vessels of the lesions were stained for beta-1 integrins, for vitronectin receptor and for molecules involved in adhesion and trans-endothelial migration of circulating leukocytes, such as ICAM-1, VCAM-1 and E-selectin. Additional findings were the observation of CD1a + multinucleated giant cells in a single case, suggesting a possible lineage relationship with the histiocytosis cells, and the demonstration of some Ki-67+ Langerhans' cell histiocytosis cells and CD1a+ mitotic figures in four of six cases, indicating local proliferation of Langerhans' histiocytosis cells.
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PMID:Expression of adhesion molecules in Langerhans' cell histiocytosis. 769 6

Langerhans' cell histiocytosis (LCH) is characterized by the presence of large mononucleated cells, associated with inflammatory cells. The Langerhans' cell (LC) lineage of the mononucleated cells is suggested by the presence of Birbeck granules and the expression of CD1a. We investigated the presence of 14 markers expressed by normal LCs in vitro. Nine skin and one lymph node frozen biopsies of LCH children were analysed by in situ immunohistochemistry. The data were compared with six skin and five lymph node frozen biopsies. LCH cells of the ten samples were positive for all 14 LC markers. We observed three different groups of markers, according to the respective staining of normal LCs and LCH cells. Group 1 included DR, DQ, CD1a, CD1c, and ICAM-3. Markers of group 1 were present on the majority of both normal LCs and LCH cells. Group 2 included CD1b, CD4, LFA-1, LFA-3, CD32, and CD68. Markers of group 2 were detected on the majority of LCH cells, but only on a fraction of normal LCs. Group 3 included CD11b, CD24, and B7/BB1. Markers of this group were detected on LCH cells, but not on normal LCs. This in situ immunohistochemical study confirms that LCH cells belong to the LC lineage. The different clinical LCH syndromes had the same immunohistochemical staining. The expression of some markers of groups 2 and 3 is known to be related to the activation of LCs in vitro. Our study suggests that LCH cells are activated LCs.
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PMID:Langerhans' cell histiocytosis cells are activated Langerhans' cells. 796 9

Intercellular adhesion molecule (ICAM)-3 is a recently described member of the immunoglobulin superfamily and, as such, is closely related to ICAM-1 and ICAM-2. All three ICAMS are cognate for the counter-receptor lymphocyte function associated antigen-1 (LFA-1, CD11a/CD18). Unlike ICAM-1 and ICAM-2, ICAM-3 is constitutively expressed at high levels on resting leucocytes. We investigated the expression and function of ICAM-3 in normal skin (n = 5), as well as its expression in psoriasis (n = 4), atopic eczema (n = 4), allergic (rhus) contact dermatitis (n = 3), and cutaneous T-cell lymphoma (CTCL, n = 2). Five-micrometre cryostat sections of skin were stained using monoclonal antibodies to ICAM-3 and a well characterized immunoperoxidase technique. In normal skin, ICAM-3 was expressed by all cutaneous leucocytes but most striking was the strong expression of ICAM-3 by Langerhans cells within both epidermis and dermis. This observation was confirmed by double-labelling with CD1a and negative staining with an IgG1 isotype control. In psoriasis, atopic eczema, allergic contact dermatitis, and CTCL, ICAM-3 was co-expressed on all CD1a+ cells, although, in psoriasis, the intensity of ICAM-3 expression was reduced. Functional blocking experiments were performed to determine whether the observed ICAM-3 expression on Langerhans cells was functionally important in antigen presentation. CD4+ T cells were prepared from peripheral blood and 10(5) CD4+ T cells combined with 10(5) epidermal cells harvested from keratome biopsies of normal skin of an individual allogeneic to the T-cell donor. Addition of 50 micrograms anti-ICAM-3 to the co-culture resulted in a consistent (50%) reduction in degree of alloantigen presentation by Langerhans cells to T cells. Inhibition was 77% of that produced by the addition of anti-LFA-1. These data indicate that ICAM-3 is constitutively expressed by Langerhans cells and is a major ligand for LFA-1 on CD4+ T cells during their response to Langerhans cells. Because fresh Langerhans cells constitutively express little ICAM-1, whereas ICAM-3 is constitutively expressed at high levels, it would appear that ICAM-3 is the dominant functional ICAM on in situ Langerhans cells in the normal epidermis.
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PMID:The ICAM-3/LFA-1 interaction is critical for epidermal Langerhans cell alloantigen presentation to CD4+ T cells. 854 30

The human dermis contains a heterogeneous network of cells with a dendritic morphology, including factor XIIIa+ dermal dendrocytes and CD34+ dendritic cells located around epidermal adnexae. Whereas dermal dendrocytes have been immunohistochemically studied, CD34+ dermal cells have not yet been well characterized. We studied by simple and double immunolabeling techniques on tissue sections of normal human skin the phenotype of these cells and found them to express vimentin and Te7 but none of the remaining markers sought (factor XIIIa, von Willebrand factor, CD1a, CD3, CD4, CD8, CD14, CD25, CD36, CD45, CD54, CD56, LFA-1, EGF-R, S-100 protein, Mac 387, and muscle-specific actin). Rare CD34+ cells of the interstitial dermis expressed human leukocyte antigen (HLA)-DR antigens, but this was not the case for periadnexal CD34+ cells. These results show that CD34+ dendritic cells of human dermis are mesenchymal cells bearing a unique immunophenotype different from that of (myo)fibroblasts, monocytes-macrophages, Langerhans cells, and factor XIIIa+ dermal dendrocytes. Whereas the involvement of CD34+ cells in some cutaneous tumors is well known, their physiologic role in normal skin remains to be established. On the basis of our results, we speculate that these cells could represent uncommitted mesenchymal cells, unique by virtue of CD34 antigen expression.
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PMID:Immunohistochemical study of CD34-positive dendritic cells of human dermis. 979 Jan 22

Actinic prurigo is an inflammatory disease of the skin that appears to be mediated by an abnormal immune response. Cell adhesion molecules play a key role in the induction of the immune response as well as in the pathogenesis of inflammation. We investigated the expression of cell adhesion and activation molecules, as well as the density of Langerhans cells in skin from patients with actinic prurigo. Skin biopsies from ultraviolet light-induced lesions, and non-irradiated areas from 10 actinic prurigo patients were studied; in addition, several spontaneous skin lesions were studied. Skin biopsies from normal individuals were used as controls. The expression of ICAM-1, ICAM-3, LFA-3, CD2, LFA-1, VLA-4, CD1a, VCAM-1, CD69, and activated b1 integrins were assessed by immunostaining. An increased expression of LFA-1, LFA-2, ICAM-3, VLA-4, and activated b1 integrins was observed in the cell infiltrate of actinic prurigo lesions and an up-regulated expression of ICAM-1 was detected in keratinocytes from these specimens. Interestingly, the number of Langerhans cells (CD1a + ) in actinic prurigo skin was not significantly affected by ultraviolet irradiation, a phenomenon that was not observed in normal controls. The increased expression of adhesion molecules in the cell infiltrate of actinic prurigo, indicates that these cells are activated and suggests that they are involved in the skin damage seen in these patients. The resistance of Langerhans cells from patients with actinic prurigo to ultraviolet light may have an important role in the pathogenesis of this condition. The involvement of keratinocytes in the pathogenesis of actinic prurigo is suggested by the expression of ICAM-1 on these cells.
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PMID:An immunohistochemical study of UV-induced skin lesions in actinic prurigo. Resistance of langerhans cells to UV light. 964 10

After UV exposure of skin, epidermal Langerhans cells (LC) are depleted, whereas CD11b+CD36 CD1a- monocytes/macrophages (UV-Mphi) infiltrate. Different immunological outcomes in vivo are mediated by LC (sensitization) and UV-Mphi (tolerance) which may be related to the distinct T cell activation states that these antigen-presenting cells (APC) induce. We previously demonstrated that CD4+ T lymphocytes activated by UV-Mphi are, in contrast to LC-activated T cells, IL-2Ralpha deficient, and we hypothesize that this differential T cell activation is related to differences in co-stimulatory molecules between UV-Mphi and LC. Using four-color flow cytometry, we found a reduced capacity to up-regulate expression of the important co-stimulatory molecules CD40, B7-1 and B7-2 by UV-Mphi relative to LC. This alteration in co-stimulatory molecule expression was selective, because UV-Mphi express equal levels of ICAM-1 and ICAM-3, and increased levels of LFA-1, relative to LC. After bidirectional signaling with T cells during alloantigen presentation, UV-Mphi still exhibited less CD40 and B7-1 than LC. Addition of IFN-gamma induced CD40 and B7-1 expression on UV-Mphi and restored IL-2Ralpha expression on UV-Mphi-activated T cells but had no effect on IL-2Ralpha on resting or LC-activated T cells. The restoration of IL-2Ralpha expression on UV-Mphi-activated T cells by IFN-gamma was inhibited (67 %, p = 0.005) by addition of neutralizing anti-CD40. Therefore, differences in co-stimulatory molecule expression, in particular CD40, on UV-Mphi and LC are critical in determining the distinct T cell activation induced by these APC.
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PMID:Low expression of CD40 and B7 on macrophages infiltrating UV-exposed human skin; role in IL-2Ralpha-T cell activation. 975 81

Epithelial Langerhans cells (LC) represent immature dendritic cells that require TGF-beta 1 stimulation for their development. Little is known about the mechanisms regulating LC generation from their precursor cells. We demonstrate here that LC development from human CD34+ hemopoietic progenitor cells in response to TGF-beta 1 costimulation (basic cytokine combination GM-CSF plus TNF-alpha, stem cell factor, and Flt3 ligand) is associated with pronounced cell cluster formation of developing LC precursor cells. This cell-clustering phenomenon requires hemopoietic progenitor cell differentiation, since it is first seen on day 4 after culture initiation of CD34+ cells. Cell cluster formation morphologically indicates progenitor cell development along the LC pathway, because parallel cultures set up in the absence of exogenous TGF-beta 1 fail to form cell clusters and predominantly give rise to monocyte, but not LC, development (CD1a-, lysozyme+, CD14+). TGF-beta 1 costimulation of CD34+ cells induces neoexpression of the homophilic adhesion molecule E-cadherin in the absence of the E-cadherin heteroligand CD103. Addition of anti-E-cadherin mAb or mAbs to any of the constitutively expressed adhesion molecule (CD99, CD31, LFA-1, or CD18) to TGF-beta 1-supplemented progenitor cell cultures inhibits LC precursor cell cluster formation, and this effect is, with the exception of anti-E-cadherin mAb, associated with inhibition of LC generation. Addition of anti-E-cadherin mAb to the culture allows cell cluster-independent generation of LC from CD34+ cells. Thus, functional E-cadherin expression and homotypic cell cluster formation represent a regular response of LC precursor cells to TGF-beta 1 stimulation, and cytoadhesive interactions may modulate LC differentiation from hemopoietic progenitor cells.
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PMID:Functional involvement of E-cadherin in TGF-beta 1-induced cell cluster formation of in vitro developing human Langerhans-type dendritic cells. 1090 41

Epithelial tissues of various organs contain immature Langerhans cell (LC)-type dendritic cells, which play key roles in immunity. LCs reside for long time periods at an immature stage in epithelia before migrating to T-cell-rich areas of regional lymph nodes to become mature interdigitating dendritic cells (DCs). LCs express the epithelial adhesion molecule E-cadherin and undergo homophilic E-cadherin adhesion with surrounding epithelial cells. Using a defined serum-free differentiation model of human CD34(+) hematopoietic progenitor cells, it was demonstrated that LCs generated in vitro in the presence of transforming growth factor beta1 (TGF-beta1) express high levels of E-cadherin and form large homotypic cell clusters. Homotypic LC clustering can be inhibited by the addition of anti-E- cadherin monoclonal antibodies (mAbs). Loss of E-cadherin adhesion of LCs by mechanical cluster disaggregation correlates with the rapid up-regulation of CD86, neo-expression of CD83, and diminished CD1a cell surface expression by LCs-specific phenotypic features of mature DCs. Antibody ligation of E-cadherin on the surfaces of immature LCs after mechanical cluster disruption strongly reduces the percentages of mature DCs. The addition of mAbs to the adhesion molecules LFA-1 or CD31 to parallel cultures similarly inhibits homotypic LC cluster formation, but, in contrast to anti-E-cadherin, these mAbs fail to inhibit DC maturation. Thus, E-cadherin engagement on immature LCs specifically inhibits the acquisition of mature DC features. E-cadherin-mediated LC maturation suppression may represent a constitutive active epithelial mechanism that prevents the uncontrolled maturation of immature LCs. (Blood. 2000;96:4276-4284)
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PMID:Ligation of E-cadherin on in vitro-generated immature Langerhans-type dendritic cells inhibits their maturation. 1111 Jul 2

Downregulation of major histocompatibility complex (MHC) class I, MHC-II, and intercellular adhesion molecule 1 (ICAM-1) expression in infected cell lines allows some viruses to escape host immunity. In skin lesions of varicella zoster virus (VZV), MHC-II transcripts were demonstrated in keratinocytes around vesicles, but not in VZV-infected cells. Whether other immunoevasive mechanisms are present during herpes zoster (HZ) is not yet elucidated. The aim of the study was to disclose the temporal immunohistochemical expression of immune escape mechanisms during HZ. Sequential skin biopsies were performed in 5 HZ patients. VZV IE63, CD1a, CD3, CD4, CD8, CD56, CD68, L1, HLA-DR, HLA-ABC, interleukin (IL)-6, IL-10, interferon gamma (IFNgamma), tumor necrosis factor alpha (TNFalpha), and ICAM-1 expressions were assessed on frozen sections using immunohistochemistry. Controls consisted of normal skin, herpes simplex virus (HSV) skin infections, and other distinct bullous skin diseases. HLA-DR and ICAM-1 expressions were not observed in VZV- and HSV-infected keratinocytes, contrasting with their upregulation in the surrounding epidermis and inside nonviral blisters. However, HLA-ABC expressions were not inhibited in VZV-infected keratinocytes. Furthermore, the CD4/CD8 ratio remained unmodified during the infection evolution, and this ratio was variable among patients. Increased IFNgamma, TNFalpha, and IL-6 expressions were present, but IL-10 expression only increased in later stages. In contrast to in vitro MHC-I and MHC-II downregulation, VZV infection is related to MHC-II but not MHC-I expression on infected keratinocytes. The absence of ICAM-1 expression on infected keratinocytes may reduce their antigen presentation capacities to LFA-1 ligand-bearing T cells. This may represent another VZV-associated immune escape mechanism. Increased IFNgamma, TNFalpha, and IL-6 expressions suggest a TH1 profile.
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PMID:Absence of intercellular adhesion molecule 1 expression in varicella zoster virus-infected keratinocytes during herpes zoster: another immune evasion strategy? 1472 20


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