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)

This study examined the influence of cytokines on surface antigen expression by gingival Langerhans cells (LC) in organ culture, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) upregulated the expression of CD1a, HLA-DR and HLA-DP antigens on LC. TNF-alpha, interleukin-4 (IL-4), and transforming growth factor beta (TGF-beta) suppressed CD29 expression, while other cytokines, including interleukin-3 and granulocyte-macrophage colony stimulating factor, were without effect. No cytokines induced CD3, CD4, CD23, CD25 or CD45 RA antigen expression in organ culture. Since TNF-alpha and IL-6 can be secreted by keratinocytes, these molecules, together with interleukin-1, are likely to play a role in the local control of LC number and function within the epithelial milleu. Thus, alterations in cytokine secretion by keratinocytes may at least in part be responsible for variations in LC number and antigen expression which occur in oral mucosal disorders.
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PMID:Modulation of Langerhans cell surface antigen expression by recombinant cytokines. 170 Nov 95

The distribution and immunophenotype of macrophages and interdigitating reticulum cells were investigated on frozen sections of seven normal thymuses and 10 thymomas. In normal thymus, macrophages were mainly located in the cortex, were markedly PAM-1+/MAC+, weakly Leu-M3+ (CD14), T4+ (CD4), T9+ and OKM-1+ (CD11b). Interdigitating reticulum cells were mainly located in the medulla and were pan-Leu+ (CD45), T4+(CD4+), HLA-DR+; furthermore, they were also often TAC+ (CD25) and T9+. Thymomas were composed of cytokeratin-containing epithelial cells admixed with variable proportions of T6+ (CD1a) lymphocytes. As defined by the histological features two thymomas were lymphocyte-rich, five were mixed type and three were epithelial-rich; eight thymomas were mainly composed of cortical epithelial cells and two were composed of spindle epithelial cells suggesting a medullary origin. In all cases, thymoma-associated macrophages were markedly PAM-1+/MAC+; they were numerous, and regularly distributed throughout the tumour. The density of macrophages per unit area was similar to that of the normal thymus, and was not influenced by the histological type or by the lymphocyte content of the tumour. Interdigitating reticulum cells were few and were confined to the areas of medullary differentiation.
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PMID:Macrophages and interdigitating reticulum cells in normal thymus and in thymoma: an immunohistochemical study. 292 78

Peptides of melanosomal proteins have recently been shown to be recognized in an HLA-restricted mode by specific cytolytic T lymphocytes in melanoma patients. Dendritic antigen-presenting cells (DC) are considered to be the most effective stimulators of T cell responses, and the use of these cells has therefore been proposed to generate therapeutic responses to tumor antigens in cancer patients. We, therefore, generated DC from peripheral blood of normal donors in the presence of granulocyte/macrophage colony-stimulating factor and interleukin-4. Flow cytometric analysis of the cells during a 2-week culture revealed a loss of CD14 and CD34 expression, a concomittent increase of CD1a, CD11a,b and c, CD44, CD45, CD54, HLA-class I and II, and intermediate levels of CD26, CD80 and CD86. Cultured DC stimulated proliferation of allogeneic T cells and induced a marked, up to 20-fold, stimulation of T cell proliferation after pulsing with tetanus toxoid. To achieve independence of already-identified antigenic peptides presented in HLA class I-restricted fashion, which limits the general applicability of such peptides for vaccination of melanoma patients, we tested whether DC are transfectable with eukaryotic expression plasmids. DC transfected with two reporter genes (CAT, beta-galactosidase) using a liposome-based transfection technique, exhibited only low levels of enzymatically active proteins, but were able to degrade rapidly intracellular proteins and to process peptides efficiently. Chloramphenicol acetyltransferase as well as tyrosinase mRNA were detectable after transfection by reverse-transcriptase-polymerase chain reaction, and enzyme activities became measurable. Furthermore, DC transfected with the tyrosinase gene were able to induce specific T cell activation in vitro, indicating appropriate peptide processing and presentation in DC after transfection. These data suggest new approaches to future tumor vaccination strategies.
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PMID:Dendritic cells generated from peripheral blood transfected with human tyrosinase induce specific T cell activation. 748 49

The cell-surface expression of the MIC2 antigen defined by the monoclonal antibody 12E7 was investigated on human leukocytes in bone marrow (BM), thymus, and peripheral blood (PB) using multiparameter flow cytometry and cell sorting. In contrast to preceding reports, we found that the MIC2 antigen is not restricted to T cells and monocytes. We show that it is also expressed in the B cell and in the granulocytic lineage, the levels of expression being related to distinct maturational stages. CD34+ cells of BM were found to express the antigen at high levels. Along the granulocytic maturation pathway from CD34+CD33+ blasts to mature granulocytes, MIC2 densities appeared progressively reduced with a considerable decline at the myelocyte stage. In B lymphopoiesis, the earliest CD34+ CD10+ B-cell precursor (BCP) cells, further subdivided by expression of CD19, displayed the highest MIC2 density of BM leukocytes. All later BCP stages showed lower MIC2 expression levels, with a remarkable reduction concomitant with loss of the CD34 antigen at the CD10+CD20- surface mu-chain- stage, and a subsequent slight upregulation along with maturation to CD10-CD20high surface mu-chain+ BCPs. The brightest MIC2 expression of all cells tested was displayed by the most immature thymic T-lineage cells characterized by the antigenic profile CD34weakor- CD7++ surface CD3-CD1a(weak) CD4weak CD8-or weak. Common thymocytes stained slightly less intense with 12E7, whereas all subsequent stages of T-lineage cells in thymus, PB, or BM showed markedly reduced MIC2 levels. Mature peripheral CD4+ as well as CD8+ T cells displayed a bimodal distribution of MIC2. In the CD4+ population, the distinct MIC2 levels were related to the well-studied functional subdivision by differential expression of CD45 isoforms, the helper-inducer/memory subset showing higher MIC2 expression than helper-suppressor/naive CD4+ T cells. Similarly high MIC2 densities were found on CD16+ natural killer cells and on CD14+ monocytes, whereas mature peripheral B cells exhibited low or intermediate expression, and granulocytes exhibited no or only dim expression. These results document that the MIC2 antigen (1) is expressed on all leukocyte lineages; (2) is differentially expressed during T- and B-lymphoid, as well as granulocytic maturation; (3) shows highest expression in the most immature lymphocytic and granulocytic developmental stages; and (4) is also differentially expressed on functional T-cell subsets. We speculate that these observations imply a functional significance of MIC2 in the network of hematopoietic adhesion pathways.
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PMID:Flow cytometric assessment of human MIC2 expression in bone marrow, thymus, and peripheral blood. 750 50

It is well established by in vivo and in vitro studies that dendritic cells (DCs) originate from hematopoietic progenitor cells. However, the presumed intermediate of Birbeck granule (BG)+ Langerhans cells (LCs) has not been detected in cultures derived from bone marrow or peripheral blood progenitor cells (PBPCs), thus contrasting with the data obtained with cord blood. We show here that large numbers of BG+ LCs can be generated from human CD34+ PBPCs in vitro, when granulocyte-macrophage colony-stimulating factor and interleukin-4, potent promotors of LC/DC differentiation, are combined with a cocktail of early acting hematopoietic growth factors. LCs were found to emerge from CD33+CD11b+CD14- progenitor cells that they share with the monocytic lineage. During culture, these cells exhibited a sequence of dramatic morphologic changes, starting with a major increase in granularity followed by an increase in size herein exceeding that of all peripheral blood cells. At the same time, CD1a and major histocompatibility complex class II expression were upregulated and virtually all CD1a++ cells were BG+ by electron microscopy. With prolonged culture, CD1a was downregulated on a major population of cells, paralleled by a loss of BG and an increase of CD4, CD25, and CD80 expression that may correspond to the maturation of epidermal LC in vitro. However, these cells were consistently CD5- and did not exhibit changes in the CD45-isoform expression during culture. The availability of large numbers of these highly purified BG+ LCs and mature DCs allows for specific analysis of these subpopulations and provides a source of potent antigen-presenting cells from individual patients for vaccination protocols against infectious or tumor-associated antigens.
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PMID:Delineation of the dendritic cell lineage by generating large numbers of Birbeck granule-positive Langerhans cells from human peripheral blood progenitor cells in vitro. 754 68

The Bcl-2 proto-oncogene regulates cell survival by antagonizing events that lead to apoptotic cell death and has been reported to be expressed in situ in lymphoid tissues, glandular epithelium, neurons, and basal epidermal cells. When we performed immunostaining on cryostat sections of normal skin, anti-Bcl-2 reactivity was confined to scattered dendritic cells in the basal epidermal layer. Double-staining experiments showed that the Bcl-2+ cells were positive for vimentin but negative for cytokeratins, CD1a, and CD45 antigens, excluding keratinocytes and Langerhans cells as possible candidates for constitutive Bcl-2 expression. Bcl-2+ epidermal cells also reacted with the monoclonal anti-melanocyte antibody NKI/beteb, and were absent from lesional skin in vitiligo, confirming that they represented epidermal melanocytes. Western blot analysis of cultured melanocytes and melanoma cell lines revealed a 26-kd protein specifically reacting with the anti-Bcl-2 monoclonal antibody. Immunostaining of pigmented lesions revealed strong expression of Bcl-2 by five of five nevocellular nevi and seven of seven melanomas. Our observations demonstrate that, within normal human epidermis, melanocytes are the only cells that express Bcl-2 constitutively and that Bcl-2 is expressed in benign and malignant pigmented tumors of the skin in situ.
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PMID:Human melanocytes and melanoma cells constitutively express the Bcl-2 proto-oncogene in situ and in cell culture. 788 47

Little is known regarding the identification, classification, and function of class II MHC+ dendritic cells in the perivasculature of human connective tissues, such as the dermis. We developed a method for preparing papillary dermal cell suspensions from human keratome strips. Among the class II MHC+ populations of the dermis identified using triple color flow cytometry, cells of monocyte/macrophage lineage (CD45+ CD1- CD11b+ CD11clo-mid CD32+ CD36+ or - CD11a-) and mesenchymal cells of non-bone marrow origin (CD45-) were identified and characterized. Another distinct class II MHC+ subset was identified, which expressed a number of features analogous to epidermal Langerhans cells (LC) and other dendritic APC. These were a numerically minor population comprising only 2.7% +/- 1% (n = 7) of dermal cells. Like LC, they express HLA-DR, CD45, CD1a (albeit at a lower level of expression), CD1c, and CD32 and lack constitutive CD11a or ICAM-1. In contrast to LC, this dermal CD1a+CD1c+ subset expresses CD1b, CD11b, a higher level of CD11c, and intracytoplasmic factor XIIIa. Alloantigen presentation by unfractionated dermal cells was reduced by prior removal of this CD1b+ subset to the same degree achieved by removal of the entire DR+ population (20% of dermal cells), indicating that this was the critical DR+ subset. Cocultures of CD4+ T lymphocytes with cells sorted by flow cytometry into CD1c+DR+, CD1c-DR+ and DR- dermal cell subsets positively identified the CD1c+DR+ population as the most potent of potential APC subsets in human dermis. Thus, in distinction to other dermal macrophage and mesenchymal subsets with elongate morphology, the CD1aloCD1b,c+CD11c(hi)CD11b+CD32+DR+ population in human dermis is highly analogous to cells of LC/dendritic APC lineage in its phenotype and in its exclusive ability to potently present Ag to T lymphocytes. These studies identify and characterize the APC subset most potent in inducing activation of T cells initially entering the perivasculature of human dermis to be of LC/dendritic APC, and not tissue macrophage, lineage.
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PMID:Heterogeneous populations of class II MHC+ cells in human dermal cell suspensions. Identification of a small subset responsible for potent dermal antigen-presenting cell activity with features analogous to Langerhans cells. 840 86

The cutaneous lymphocyte associated antigen (CLA) recognized by the monoclonal antibody (moAb) HECA-452 plays a major role in the homing of lymphocyte subpopulations to the skin by binding to E-selectin on dermal microvessels. The factors responsible for the immigration of Langerhans cells (LC) and their precursors into the skin are still unknown, but because normal resting LC are also capable of expressing CLA, the antigen was proposed as a candidate LC-homing structure. To gain insight into these mechanisms, the expression of HECA-452 on neoplastic LC within and outside the skin was investigated in paraffin-embedded sections from 44 patients with localized and disseminated forms of Langerhans cell histiocytosis (LCH) presenting with proliferating cells positive for CD45, CD1a, S100 and HLA-DR. Irrespective of the clinical presentation or the type of organ involved, HECA-452 positive LC were detected in all biopsies tested (range 5->90%). The most prominent HECA-452 reactivity was observed in skin lesions and in areas with accumulations of eosinophilic granulocytes. Our data provide evidence for heterogeneous expression of sLex/sLea structures in various stages of activated and/or differentiated LCH cells. Remarkably, CLA-antigen expression on LCH-cells was not restricted to cutaneous sites. In view of recent findings on the expression of HECA-452 on resting epidermal LC, our data are compatible with the view that local cytokine production by keratinocytes or cells from the surrounding infiltrate induce and/or modulate CLA expression on LC in both cutaneous and extra-cutaneous sites.
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PMID:Expression of the monoclonal antibody HECA-452 defined E-selectin ligands in Langerhans cell histiocytosis. 862 76

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

Dendritic cells (DC) are the most potent APCs within the immune system. We show here that highly purified CD14(bright) peripheral blood monocytes supplemented with granulocyte-monocyte (GM)-CSF plus IL-4 develop with high efficacy (>95% of input cells) into DC. They neo-expressed CD1a, CD1b, CD1c, CD80, and CD5; they massively up-regulated CD40 (109-fold) and HLA-DQ and DP (125- and 87-fold); and significantly (>5-fold) up-regulated HLA-DR, CD4, CD11b, CD11c, CD43, CD45, CD45R0, CD54, CD58, and CD59. CD14, CD15s, CD64, and CDw65 molecules were down-regulated to background levels, and no major changes were observed for HLA class I, CD11a, CD32, CD33, CD48, CD50, CD86, CDw92, CD93, or CD97. Monocytes cultured in parallel with GM-CSF plus TNF-alpha were more heterogeneous in expression densities but otherwise similar in their surface molecule repertoire. They clearly differed, however, in their accessory cell capacity. Only GM-CSF plus IL-4-cultured cells were found to be potent stimulators in allogeneic and autologous MLR and they presented tetanus toxoid 100- to 1000-fold more efficiently than other cell populations tested. Furthermore, only cytokine-treated monocytes formed clusters with resting T cells. At variance from all these similarities between in vitro-generated monocyte-derived DC and in vivo-developing DC, the DC populations generated by us contained significant amounts of myeloperoxidase and also expressed lysozyme. At least in this respect they, thus, differ from "classical" DC types.
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PMID:Molecular and functional characteristics of dendritic cells generated from highly purified CD14+ peripheral blood monocytes. 889 15


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