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)

The cellular and molecular events taking place during epidermal antigen exposure in sensitized individuals are principally well understood. Epidermal Langerhans cells (LC) are supposed to take up, process, and express a given foreign substance on their cell surface. The antigen is then recognized by T cells bearing the appropriate T-cell receptor (TCR). Because LC do not bear variable antigen (Ag)-specific binding sites, one could postulate that the epidermal exposure of any substance should activate LC and other cells of the skin immune system. To test this hypothesis, we analyzed immunophenotypically the cellular trafficking events in positive (n = 5) and negative epicutaneous patch-test reactions (n = 10), using a panel of monoclonal antibodies against CD1a, CD11c (Ki-M1, LeuM5), CD68 (Ki-M6), Ki-M8, and CD3 (Leu4). We can demonstrate that irrespective of whether or not an antigen will be responded to by the immune system (i.e., positive or negative test reaction), epidermal antigen exposure causes a decrease of LC density in the epidermis and simultaneously causes an increase of LC in the dermis. Moreover, monocytes and T cells immigrate into the dermis both in positive and negative patch-test reactions. As is to be expected, the degree of this cellular traffic is more pronounced in positive test reactions, which may be due to amplification mechanisms caused by antigen recognition of sensitized T cells. This finding demonstrates that human skin contains cell migration programs that ensure that any foreign substance will be accessible to the skin immune and phagocytic system.
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PMID:Cell trafficking in positive and negative patch-test reactions: demonstration of a stereotypic migration pathway. 167 41

A detailed immunologic study of three cases of sinus histiocytosis with massive lymphadenopathy (SHML) was performed to better characterize this rare disorder. One patient had prominent cervical lymphadenopathy that regressed spontaneously, whereas the other two patients had persistent cervical lymphadenopathy and recurrent infections. The first patient was otherwise healthy and had normal immunologic studies. One of the latter patients had a relative increase in blood B cells, a decreased level of serum immunoglobulin A (IgA), decreased blood lymphocyte mitogenic responses to multiple mitogens (37-42% of controls), and cutaneous anergy. The other patient with persistent disease also had a relative increase in blood B cells, polyclonal hypergammaglobulinemia, and circulating immune complexes, as well as decreased blood T cells and markedly decreased blood lymphocyte responses to mitogens (12-37% of controls). Immunohistochemical stains of the lymph nodes of the three patients revealed a characteristic phenotype for the sinus histiocytes: S-100 protein, 3/3; CD14 (Leu M3) 3/3; CD11c (Leu M5), 1/1; CD71 (OKT9), 3/3; CD4 (Leu 3a), 2/3; CD1a (OKT6), 1/3; alpha-1-antitrypsin, 3/3; alpha-1-antichymotrypsin, 3/3; CD35 (C3b), 1/1; CD11b (Mo1), 0/3; CD15 (Leu M1), 0/3; HLA-DR, 0/3; and lysozyme, 0/3. This phenotype suggests that the cells of SHML have features of both the Langerhans/interdigitating cell and mononuclear phagocyte lineages. Emperipolesis by the histiocytes of B cells, T cells, and natural killer cells was demonstrated by a double-staining technique. Our findings indicate that patients with SHML may have a variably expressed immunodeficiency that predisposes them to recurrent infections.
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PMID:Sinus histiocytosis with massive lymphadenopathy: a spectrum of disease associated with immune dysfunction. 171 75

The immunophenotypic properties of the abnormal cells in routine specimens from 16 cases of Langerhans cell histiocytosis (LCH) were examined. In five cases, cryostat sections were also available. The abnormal cells expressed a similar phenotype and were positive for HLA-DR, S-100 protein, peanut agglutinin (PNA), CD1a, CD4 and several macrophage-associated markers, including CD11c, CDw32 and CD68 (the latter detectable in routine sections with antibody KP1). Staining with CD14, CD35 (C3b receptor), and CD11b (C3bi receptor) was negative with the exception of one of the cases in which a proportion of the cells showed faint positivity with CD11b. Staining for pan-T-cell (CD2, CD3, CD5) and pan-B-cell (CD19, CD22) antigens was negative in all lesions. It is concluded that LCH expresses a characteristic phenotype with some heterogeneity with regard to macrophage markers and that immunohistochemical methods in cryostat sections and routine specimens form a useful supplement to other techniques for the diagnosis of this condition.
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PMID:Immunohistochemical study of the abnormal cells in Langerhans cell histiocytosis (histiocytosis x). 210 27

We have investigated the features and distribution of accessory cells (ACs) and the relationship of these cells to each other and to lymphocytes in the epithelium and lamina propria of oral hairy leukoplakia (HL), with the objective of better defining the differentiation and mutual interactions of immune-response cells within HL as a preliminary step to understanding the onset and significance of this lesion during human immunodeficiency virus (HIV) infection. Twenty-four HIV-infected patients with HL, two asymptomatic HIV-positive subjects, and three HIV-negative subjects were studied by immunohistochemistry; five HIV-positive patients with HL and three asymptomatic HIV-positive subjects were studied by electron microscopy. In both the epithelium and the lamina propria of HL, we found cells with the immunohistochemical and ultrastructural features of variably differentiated ACs; differences were found between the epithelium and lamina propria. In the lamina propria, ACs were characterized by dendritic shape, multiple contacts with lymphocytes, expression of CD1a antigen, and ultrastructural features of fully differentiated ACs. Conversely, in the epithelium ACs showed bluntly dendritic shape, low expression of CD1a, absent expression of HLA-DR, constant expression of CD11c and CD14 antigens, only occasional contacts with lymphocytes, and ultrastructural features of variably, but always incompletely, differentiated cells of monocyte-dendritic lineage. Seventy-nanometer wide intracisternal particles, closely resembling A particles described in retroviral infections, were found in the intraepithelial ACs in two patients with HL. The defective differentiation of ACs in the epithelium of HL--possibly influenced by the perturbation of the epithelial microenvironment induced by Epstein-Barr virus, and following the direct HIV infection of these cells--and the exceptional finding of close contacts with lymphocytes suggest that the lesional epithelium of HL may constitute a pathway for the entry of foreign antigens which circumvent monitoring by ACs and can induce immune tolerance. The impairment of the local immune response in HL may contribute to the development of full blown, systemic immunodeficiency.
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PMID:Morphology and membrane antigens of nonlymphoid accessory cells in oral hairy leukoplakia. 239 34

Bone marrow cells of a patient with Letterer-Siwe disease were cultured for three weeks in long-term bone marrow culture (LTBMC) conditions and examined at one-week intervals with a large panel of monoclonal antibodies by immunohistochemistry and by the immunogold transmission electron microscopy (immunoTEM) technique. Although at diagnosis the bone marrow showed a slight increase of monocytes with a normal phenotype, a rapid expansion of cells expressing CD1a and CD1c was observed already after 1 week of culture. A progressive increase in CD4, CD11b and CD11c expression was also observed. ImmunoTEM of cultured cells demonstrated that CD1a+ cells had macrophage-like morphology, and did not contain Birbeck granules. These findings indicate that bone marrow monocytes acquire some phenotypical features of Langerhans cells in LTBMC and support the hypothesis that these cells may derive directly from a bone marrow monocytic precursor.
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PMID:Bone marrow monocytes in histiocytosis X acquire some phenotypic features of Langerhans cells in long term bone marrow cultures. 247 66

Epidermal Langerhans cell heterogeneity is poorly understood with regard to phenotypic characteristics, such as the expression of human leukocyte antigen (HLA)-DR, integrin, and Fc receptor molecules, as well as functional characteristics, such as the ability to process and present antigens or produce cytokines during various phases of immigration and maturation. Technical limitations of Langerhans cell number have limited functional assays on putative Langerhans cell subsets in in vivo epidermis. Therefore, we used flow cytometry for simultaneous phenotypic and functional assessment at the single-cell level within the Langerhans cell population. Freshly isolated human epidermal cell suspensions were stained with a battery of monoclonal antibodies, including anti-HLA-DR, -CD1a, -CD1c, -CD11c, -Fc gamma RII, and -Fc epsilon RI. Two distinct Langerhans cell subsets were identified by their different levels of HLA-DR expression. The DRHi subset expressed higher amounts of CD11c and exhibited greater cytoplasmic complexity and higher baseline calcium than the DRLo subset (p < or = 0.03 for each). Some subjects also expressed high levels of Fc epsilon RI in the DRHi, CD11cHi subset. To determine whether these phenotypic subsets may exhibit differential signal-transduction functional properties, Langerhans cells were partially enriched over Ficoll-Hypaque and their cytosolic mobilization after the addition of ionomycin was analyzed using the calcium indicator, indo-1, in conjunction with quantitative analysis of HLA-DR expression. By this real-time flow cytometric analysis, a new subpopulation was revealed within the DRLo Langerhans cell subset. This subset increased its cytosolic calcium concentration much more than the other two subsets (change in indo-1 blue:violet emission ratio of 37.33 +/- 2.34 in the Hi Flux DRLo subset versus 13.23 +/- 0.29 in the Lo Flux DRLo subset, and versus 7.6 +/- 2.99 in the Lo Flux DRHi subset). These data indicate that functional, as well as phenotypic, subsets of Langerhans cells exist within normal human epidermis. Their responses to physiologic stimuli may relate to maturational stage or the level of in vivo activation.
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PMID:Differential responsiveness of Langerhans cell subsets of varying phenotypic states in normal human epidermis. 752 45

A 71-year-old Japanese woman had two dome-shaped tumors on her right buttock with several surrounding papules. Histological examination revealed that large anaplastic cells and atypical lymphoid cells densely infiltrated the entire dermis. On immunohistochemical examination, Ki-1, HLA-DR, CD25 (IL-2 receptor alpha), CD122 (IL-2 receptor beta), CD4, CD11c and CD68 were all positive in the tumor cells, whereas CD1a, CD3, CD5, CD8 and CD19 were negative. Neither rearrangement of the T-cell receptor beta, T-cell receptor gamma nor the immunoglobulin heavy-chain was seen. Ultrastructurally, most of the tumor cells contained thick bundles of intermediate filaments in the perinuclear cytoplasm. Thus, this patient was diagnosed as having Ki-1-positive lymphoma of non-T, non-B origin. No recurrence or metastasis of the tumor has been observed in the last 2 years, although surgical resection was required 3 times before control was achieved.
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PMID:Primary cutaneous CD30(Ki-1)-positive lymphoma of non-T, non-B origin. 759 89

A case study of sinus histiocytosis of Rosai-Dorfman (SH) clinically limited to the skin is presented with immunohistochemical study of the infiltrate, in both paraffin and cryostat sections. Factor XIIIa, a dendrocyte marker, was demonstrated in the cytoplasm of histiocytes. This feature had not been previously reported in this disease. In addition, the cells expressed S100 protein, CD4, CD1a, CD68, and CD11c. This immunophenotyping study suggests that SH could affect the antigen-presenting activity of Factor XIIIa cells, i.e., the skin dermal dendrocyte.
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PMID:Sinus histiocytosis (Rosai-Dorfman disease) clinically limited to the skin. An immunohistochemical and ultrastructural study. 769 80

Macrophages play important roles in immunity and inflammation, and in allergic, granulomatous and neoplastic diseases. Here, we present the indepth results of an ongoing study of macrophage differentiation pathways in cutaneous macrophage disorders and in vitro. Up to now, a total of 40 cases of cutaneous macrophage disorders (histiocytoses and granulomas) and related diseases were examined using a panel of monoclonal and polyclonal antibodies to macrophage differentiation antigens (mAb MS-1, mAb alpha CD1a, mAb alpha CD34, mAb RM 3/1, mAb alpha CD11c, mAb alpha CD36, mAb MAC 387, mAb 27E10, polyclonal antibodies alpha MRP-8 and -14, mAb alpha CD68, mAb 25F9, mAb DRC1-R4/23, and mAb 1F10). Of these, MS-1 high molecular weight protein, synthesized by non-continuous sinusoidal endothelial cells and highly dendritic perivascular macrophages in normal human organs, is the most specific macrophage differentiation marker. MS-1 high molecular weight protein is selectively expressed by cutaneous non-Langerhans cell histocytoses, and proves to be a valuable diagnostic tool for these diseases. MS-1 high molecular weight protein is not found in Langerhans cell histiocytosis cells, epithelioid cells in sarcoidosis, and palisading histiocytes in granuloma annulare. MS-1+ macrophages may be found intermingled in cellular type dermatofibroma and in foreign body granulomas; they differ from MS-1+ non-Langerhans cell histiocytosis cells by their highly dendritic morphology, and thus rather resemble the MS-1+ macrophages in normal skin. RM 3/1 antigen shows a similar, but broader expression pattern including non-Langerhans cell histiocytoses, xanthelasmata palpebrarum, foreign body granulomas, granuloma annulare, and cellular type dermatofibroma. Moreover, xanthelasmata palpebrarum paradigmatically represent a class of macrophage lesions with strong RM 3/1, but little MS-1 antigen expression. In sarcoidosis, RM 3/1+ macrophages are only found at the very periphery of epithelioid cell granulomas. In contrast, 25F9 antigen is strongly and consistently expressed in epithelioid cells of sarcoidosis, and in foreign body granulomas. In cultured human monocytes/macrophages, RM 3/1 antigen is expressed early on, while MS-1 high molecular weight protein and 25F9 antigen are late and very late macrophage differentiation antigens, respectively. Expression of RM 3/1 antigen and MS-1 high molecular weight protein is inducible by glucocorticoid and interleukin-4, and less so by interleukin-13 and interleukin-10, and combinations thereof, while 25F9 antigen seems to be less influenced by these agents. Interferon-gamma (and less so tumor necrosis factor-alpha) inhibit expression of all three antigens in cultured human monocytes/macrophages.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dissection of macrophage differentiation pathways in cutaneous macrophage disorders and in vitro. 774 70

Immunomodulatory effects of retinoids may be part of their anti-carcinogenic and anti-inflammatory properties. We studied the in vivo effects of retinoic acid (RA) on antigen-presenting activity of human epidermal Langerhans cells and on accessory cell activity of keratinocytes. Two skin sites from each volunteer were treated in vivo with 0.1% RA or vehicle, respectively, once a day for 4 d. RA-treated epidermal cell (RA-EC) alloantigen presentation to CD4+ T cells in each volunteer tested was consistently greater than that induced by vehicle EC. However, this increased antigen-presenting activity did not lead to autoreactive CD4+ T-lymphocyte proliferation. Elevated unfractionated epidermal antigen-presenting activity of RA-EC was not due to increased keratinocyte major histocompatibility complex (MHC) or intercellular adhesion molecule expression or to other keratinocyte accessory signaling, because incubation of CD1a-fluoroscence-activated cell sorter (FACS)-purified RA-EC inhibited alloantigen presentation, presumably through increased keratinocyte transforming growth factor-beta. By contrast, Langerhans cell function was upregulated; FACS-purified CD1a+ Langerhans cells derived from RA-EC displayed a markedly increased ability, relative to Langerhans cells from vehicle EC, to present alloantigen to T cells. Triple color flow-cytometric analysis of RA-EC and vehicle EC suspensions revealed that RA treatment did not modify the number of DR+ and CD1a+DR+EC, but did result in statistically significant increases in Langerhans cells expression of HLA-DR, CD11c, and CD1c. Another novel finding was that HLA-DR-dependent Langerhans cells antigen-presenting activity in both normal and RA-treated skin was completely blocked by anti-CD11c antibody. Thus, retinoid upregulation of antigen-presenting activity may be due to upregulation of Langerhans cell CD11c, as well as class II MHC. Upregulation of cutaneous immune responsiveness in human skin without autoreactivity has not (to our knowledge) been reported previously, and the Langerhans cell phenotypic and functional state achieved is distinct from previously reported states of Langerhans cell activation.
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PMID:Retinoic acid upregulates human Langerhans cell antigen presentation and surface expression of HLA-DR and CD11c, a beta 2 integrin critically involved in T-cell activation. 779 14


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