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

Dendritic cells are considered to be the initiators of immune responses, including those directed against tumors. Clinical research on dendritic cells was long hampered by the limited availability of these cells. The recent identification of cytokine combinations that mobilize dendritic cells with potent antigen-presenting cell function from peripheral blood represented a major progress. We show in this study that substantial numbers of dendritic cells can be obtained from the peripheral blood of patients with renal-cell carcinoma. The procedure requires a relatively small blood sample (40 ml) and avoids both priming of the patient with granulocyte-colony stimulating factor and leukapheresis. Approximately 2 to 8 million cells with the characteristics of dendritic cells could be obtained: phase-contrast microscopy revealed the typical cytoplasmic processes or veils; phenotypic analysis confirmed expression of dendritic-cell-associated molecules, including MHC class II, CD1a, CD4, ICAM-1 (CD54), LFA-3 (CD58), B7-1 (CD80) and B7-2 (CD86), and absence of T-cell, B-cell and monocyte markers; in addition, these cells rapidly attached to and migrated on collagen-type-1-coated surfaces. Interestingly, attachment was accompanied by acquisition of the CD14 antigen; functionally, cultured dendritic cells proved to be very potent co-stimulators of the phytohemagglutinin-induced proliferation of autologous tumor-infiltrating lymphocytes. The reproducible growth of functional dendritic cells from cancer patients is encouraging for the design of immunotherapy protocols.
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PMID:Dendritic antigen-presenting cells from the peripheral blood of renal-cell-carcinoma patients. 759 Dec 77

The skin is not only a physico-mechanical barrier between the environment and the body, but it also functions as an immune organ. The immunological function of epidermis is principally linked to the presence in this tissue of a distinct subpopulation of dendritic cells: the Langerhans cells (LC). LC constitute 2-4% of epidermal cell population and within epidermis they are the only cells which express MHC class II antigens constitutively. LC play a key role in the initiation of T cell responses to cutaneous antigens by picking up the antigen and migrating to the draining lymph node where they trigger specific T cell activation. There is also evidence that keratinocytes participate in immune responses in the skin since these cells produce a wide variety of cytokines that can modulate T cell responses. Dendritic cells comprise a system of highly efficient antigen-presenting cells which initiate immune responses such as the sensitization of T cells restricted by major histocompatibility complex molecules, the rejection of organ transplants and the formation of T-cell-dependent antibodies. Dendritic cells are found in many non-lymphoid tissues, such as skin and mucosa (Langerhans cells), and they migrate after antigen capture through the afferent lymph or the bloodstream to lymphoid organs, where they efficiently present antigen to T cells. Dendritic cells are difficult to isolate and, although they originate from bone marrow their growth and differentiation are still poorly characterized. Granulocyte macrophage-colony stimulating factor (GM-CSF) favours the out-growth of dendritic cells from mouse peripheral blood. The cooperation between GM-CSF and tumour necrosis factor-alpha (TNF-alpha) is crucial for the generation of human dendritic/Langerhans cells from CD34+ haematopoietic progenitors. The availability of large numbers of these cells should now facilitate the understanding of their role in immunological regulation and disorder. Recent studies reported that after 2-3 days in vitro incubation, both murine and human LC undergo profound phenotypic changes, as an enhancement in the expression of MHC class I and II antigens, LFA-3 and ICAM-1 molecules, a concomitant decrease of CD1a antigens and a loss of Fc gamma RII. Furthermore, cultured LC (cLC) lose or markedly reduce their specific cytoplasmic organelles: the Birbeck granules. Therefore, after a 2-3 days in vitro incubation, LC seem to acquire most of the features of lymphoid dendritic cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Cutaneous immune system]. 783 4

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

By means of microsurgical lymph cannulation human skin lymph derived from the late phase of an elicitation reaction to diphenylcyclopropenone was sampled. Cells were isolated by centrifugation and then treated with mouse anti-CD1a monoclonal antibodies and sheep antimouse antibody-coated Dynabeads. Ultrastructural and immunocytochemical analyses revealed anti-CD1a/Dynabead-rosetted CD1a- and protein S-100-positive cells which did not express monocyte surface markers, but surface antigens such as HLA-DR, ICAM-1 and, in part, LFA-3. In comparison to freshly prepared human epidermal Langerhans cells (LC), a large fraction of these cells contained no or markedly fewer Birbeck granules and exhibited extensive ruffling of the surface. These data suggest that the phenotype of LC in skin lymph derived from the elicitation phase of allergic contact dermatitis is similar to LC cultured in vitro. In the functional concept of LC of our time, these cells correspond to the dendritic cells designated as "veiled".
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PMID:Phenotype of Langerhans cells in human afferent skin lymph derived from allergic contact dermatitis. 816 48

Ultraviolet (UV) radiation impairs cutaneous immune functions and induces antigen-specific tolerance both locally at the irradiated skin site, as well as at distant skin sites and systemically. It has been postulated that in the local model, altered Langerhans' cells (LC) provide tolerogenic signals, and studies in vitro have indicated that UV radiation may down-regulate the expression of co-stimulatory molecules on the surface of these cells. To examine the effect of UV radiation on LC co-stimulatory molecules in vivo, we irradiated human volunteers with erythematogenic doses of solar-simulating UV radiation (SSR), and analyzed the expression of cell surface markers in dermatome skin samples obtained 1-72 h post-irradiation. For flow cytometric analysis, epidermal cell (EC) suspensions were prepared and double labeled with monoclonal antibodies against CD1a or HLA-DR, and B7-1 (CD80), B7-2 (CD86), ICAM-1 (CD54), ICAM-3 (CD50), LFA-3 (CD58), E-cadherin, or integrin-beta4 (CD104). In unirradiated control skin samples, keratinocytes (KC) expressed high levels of E-cadherin. LC expressed high levels of both E-cadherin and ICAM-3, and low levels of B7-2, LFA-3, ICAM-1, and integrin-beta4. Following SSR, a triphasic reaction pattern was seen: an immediate, down-regulatory phase prevailing 2-6 h post-irradiation, when the number of DR+ and CD1a+ cells were temporarily reduced; a delayed, up-regulatory phase in which the number of LC was increased and the expression intensities of CD1a, HLA-DR, B7-1, and B7-2 were strongly up-regulated, maximally evident 12-24 h after irradiation, but no more seen at 48 h; and a late phase at 72 h, in which an influx of monocytes and a concomitant rise in DR+ cells was recorded. We conclude that to understand real-life cutaneous UV immunology, studies in vitro need to be complemented with studies in vivo. In the case of LC, the effects of erythematogenic UV radiation in vivo on human LC B7 co-stimulatory molecules include an up-regulatory stage.
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PMID:Up-regulation of human epidermal Langerhans' cell B7-1 and B7-2 co-stimulatory molecules in vivo by solar-simulating irradiation. 913 Jun 54

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

High expression of MHC antigens and adhesion/costimulation molecules is considered as one of the major characteristics qualifying macrophages (M) and dendritic cells (DC) as professional antigen presenting cells. Since accessory activity of M is known to be weaker than that of DC but both M or DC can differentiate from blood monocytes (MO) depending on culture conditions (i.e. GM-CSF vs GM-CSF/IL-4), we investigated the kinetics of expression of MHC antigens and several adhesion/costimulation molecules during the differentiation of DC or M from blood MO. Blood MO cultured with GM-CSF consistently induced M that showed adherence to plastic and CD14 expression. In contrast, MO cultured with GM-CSF/IL-4 rapidly became nonadherent, acquired DC morphology and lost CD14 expression. M but not DC proliferated as demonstrated by [H3]thymidine incorporation. MHC Class I was highly expressed in both M and DC. In contrast, MHC Class II molecules were significantly higher on DC compared to M. CD80 was upregulated on both DC and M but only on a subset of cells. CD80 expression peaked at day 3 on M and declined thereafter, while on DC expression increased significantly until day 10. CD86 was upregulated on the majority of DC and M. However, while M maintained stable expression of CD86 after day 3, DC progressively upregulated CD86 throughout the culture period. CD1a expression was initially low in both cell types and peaked at day 3 in M declining thereafter, while expression remained stable on DC until day 10. ICAM-1 expression was significantly upregulated on M when compared to DC at day 3. However, on M, ICAM-1 expression became undetectable by day 5 while on DC it increased through day 10. Similarly, CD40 was transiently expressed on M until day 5, while on DC it continuously increased until day 10. Finally, in contrast to other antigens, LFA-3 was always more strongly expressed on M than DC at all culture periods. Taken together, these data suggest that M showed a rapid but transient upregulation in the expression of adhesion/costimulation molecules, suggesting that maximal accessory ability is reached by M at an earlier time point than DC. Significant differences in surface antigen expression DC vs M were recognizable for MHC class II, CD86, CD80, CD1a, CD40 and ICAM-1. Specifically, major differences occurred for MHC class II, CD86, CD40 and ICAM-1. Therefore, the higher accessory ability of DC compared to M in naive T cell priming may be related to qualitative and quantitative differences in expression of these immunologically important surface molecules.
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PMID:Expression of surface antigens during the differentiation of human dendritic cells vs macrophages from blood monocytes in vitro. 1041 27

Vasculitic neuropathy and chronic inflammatory demyelinating polyneuropathy (CIDP) are neuropathies characterized by a T-lymphocyte infiltrate in the peripheral nerves. The microenvironment in which these T cells become activated, and the molecules and cells that play a role in this process are incompletely understood. Using immunohistochemical analysis, we studied the effect of the presence of adhesion, costimulatory and antigen-presenting molecules on different cell types as a precondition for local T-cell activation in human sural nerve biopsies of seven patients with CIDP, three patients with vasculitic neuropathy and three healthy controls. In biopsies from CIDP and vasculitic neuropathy patients, but not in those from healthy controls, Schwann cells expressed the adhesion/T-cell stimulatory molecule CD58 (LFA-3). The CD58 molecule was also present on endothelial cells of all vasculitic neuropathy patients and one CIDP patient. In biopsies from normal controls and patients, CD54 (ICAM-1) expression was detectable on microvascular endothelial cells. In addition, expression of the costimulatory molecule CD86 was detected on vascular tissue in patients with vasculitic neuropathy. Although macrophages were always present in all subjects, expression of the major histocompatibility complex (MHC)-like molecule CD1a by macrophages was restricted to biopsies from two CIDP patients and one vasculitic neuropathy patient. Unexpectedly, Schwann cells of a single vasculitis patient strongly expressed CD1b, a molecule involved in the presentation of self-glycolipids to T cells. Schwann cells in biopsies from patients and normal controls expressed high levels of the invariant chain, CD74, a molecule involved in the intracellular sorting of MHC class II molecules. There was no evidence for the presence of dendritic cells in sural nerve biopsies. These findings support a model in which T-cell activation can be initiated and/or perpetuated locally in sural nerve biopsies of patients with CIDP and vasculitic neuropathy, and predict an important role for Schwann cells and endothelial cells.
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PMID:Expression of accessory molecules for T-cell activation in peripheral nerve of patients with CIDP and vasculitic neuropathy. 1100 19

Dendritic cells (DCs) are present in essentially every mammalian tissue, where they operate at the interface of innate and acquired immunity by recognizing pathogens and presenting pathogen-derived peptides to T lymphocytes. According to the research group of Shortman, experimental results suggest a "dual" DC differentiation model, demonstrating the existence of both myeloid-derived (with characteristic IF: CD11b+, CD11c+, CD8alpha- and DEC205+) and lymphoid-derived DCs (showing CD11b- CD11c-, CD8alpha+ and DEC205+ IF). DCs, including interdigitating cells (IDCs) and Langerhans cells (LCs), are characterized by dendritic morphology, high migratory mobility and are the most effective, "professional" cells for antigen presentation in primary immune responses. Most of the DCs express immunocytochemically detectable antigens like: S-100, CD1a, CD40 receptor, adhesion molecules (ICAM-1 or CD54, LFA-1 and LFA-3), integrins (CD11a, CD11c and CD18), CD45, CD54, co-stimulatory molecules (B7-1 or CD80, B7-2 or CD86), F418, MHC class I and II and DEC-205, multilectin receptor, immunostimulatory cytokine (IL-12) and, of course, Fc and complement receptors. Following recognition and uptake of antigens, mature dendritic cells (DCs) migrate to the T lymphocyte rich area of draining lymph nodes, display an array of antigen-derived peptides on the surface of major histocompatibility complex (MHC) molecules and acquire the cellular specialization to select and activate naive antigen-specific T lymphocytes. Immunotherapeutic ideas are based on the ability of the mammalian immune system to recognize neoplastically transformed cells. Immunotherapy of human neoplasms has always represented a very attractive fourth-modality therapeutic approach, especially in light of the many shortcomings of conventional surgical, radiation and chemotherapies in the management of neoplastically transformed cells. The cancer vaccine approach to therapy is based on the notion that the immune system could possibly mount a rejection strength response against the neoplastic cell conglomerate. The efficiency of DCs for T lymphocyte stimulation moved a number of research groups to develop DC- based immunotherapy approaches. The failure of cancer vaccines may be attributed to the relationship between host and neoplasm: through a natural selection process, the host facilitates the selective enrichment of clones with highly aggressive neoplastically transformed cells, being in various stages of differentiation and only during certain stages express neoplastic cell specific molecules.
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PMID:Antigen presentation by dendritic cells and their significance in antineoplastic immunotherapy. 1501 56


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