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)

Colonies of CD1a+ HLA-DR+/DQ+ CD4+ cells with the functional and some of the structural attributes of Langerhans cells are observed in human bone marrow cultures in semi-solid media and are assumed to be the progeny of an early progenitor, the dendritic/Langerhans cell CFU (CFU-DL). The cytokine-regulated growth of these cells has been studied using a chemically defined serum-free system to culture both unfractionated and highly enriched bone marrow progenitor cell populations. Although unfractionated cell growth was optimal in serum replete cultures with PHA-stimulated leukocyte-conditioned medium (PHA-LCM) suboptimal proliferation of CFU-DL was observed in serum even in the absence of PHA-LCM. No colonies were observed under serum-free conditions when granulocyte-macrophage CSF (GM-CSF), IL-3, granulocyte CSF (G-CSF), and macrophage CSF (M-CSF) were present at levels optimal for granulocyte colony-forming unit (CFU-G) and macrophage colony-forming unit (CFU-M) growth. Addition of IL-1 alpha to these cytokines stimulated a small number of CFU-DL. However, in the presence of GM-CSF and IL-3, TNF-alpha or TNF-beta (5 U/ml) were both highly effective in promoting growth up to 82% of optimal and CFU-G growth was also enhanced at these concentrations. TNF was only active during the first 3 days of culture and higher concentrations of TNF-alpha but not TNF-beta were inhibitory for both CFU-DL and CFU-G. CD34+ cell-enriched populations were also enriched for both myeloid progenitors (CFU-G + CFU-M) and CFU-DL to 36- and 48-fold, respectively, and single cell cultures of CD34+ cells yielded single colonies containing both CD1a+ dendritic cells and CD1a- macrophages. Thus dendritic/Langerhans progenitors in the bone marrow expresses CD34, have a capacity for both macrophage and dendritic cell differentiation, and depend on hemopoietic growth factors and TNF for their further development in vitro.
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PMID:Interactions of tumor necrosis factor with granulocyte-macrophage colony-stimulating factor and other cytokines in the regulation of dendritic cell growth in vitro from early bipotent CD34+ progenitors in human bone marrow. 138 22

Langerhans cells (LC) undergo a variety of phenotypic and functional changes in vitro. To determine the effects of granulocyte macrophage--colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha), and interleukin 1-alpha (IL-1) on LC phenotype in vitro, epidermal cell suspensions were enriched for LC by density-gradient centrifugation and cultured in the presence of 10 ng/ml of these cytokines. The percentage of cells expressing the surface protein CD1a was determined by flow cytometry. This percentage typically dropped after 48 h culture in both control and cytokine-treated medium to less than half that of the starting value. By the fifth day, the percentage of cells expressing CD1a in TNF-alpha and IL-1--treated cultures was still near half of the starting value, slightly above that of control cultures. Treatment with GM-CSF caused large and consistent decreases in the percentage of epidermal cells expressing CD1a. Cell viability in each of the three cytokine-treated cultures was identical to the control cultures, with essentially all cells having died by the sixth day after isolation. To determine the functional effects of these cytokines, the cytokine-containing medium was replaced after 72 h with medium containing purified allogeneic T cells and proliferation measured. Preliminary experiments showed no increased proliferation induced by IL-1 or TNF-alpha--treated epidermal cells. GM-CSF-treated epidermal cells induced 2-3 times more T-cell proliferation than epidermal cells cultured without additional cytokines. We conclude that GM-CSF, a cytokine known to be produced by keratinocytes in vitro, decreases CD1a expression by human LC and increases their ability to stimulate proliferation by allogeneic T cells.
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PMID:Granulocyte macrophage--colony-stimulating factor (GM-CSF) decreases CD1a expression by human Langerhans cells and increases proliferation in the mixed epidermal cell-lymphocyte reaction (MELR). 169 5

Recent immunohistochemical investigations of thyroid carcinomas have revealed that dense infiltration by dendritic cells (DCs) is correlated with a favorable prognosis. The present study was done to clarify the frequency and characteristics of DC infiltration in thyroid carcinomas, and also cytokines associated with DC maturation and migration. Compared with follicular carcinomas, papillary carcinomas contained significantly higher numbers of DCs, interleukin (IL)-1 alpha- and tumor necrosis factor (TNF)-alpha-positive cells, and cells positive for two TNF-alpha receptors (p60 and p80). The centers of cancer nodules had large numbers of CD1a- and CD1c-positive DCs suggesting that they were Langerhans cells, whereas the periphery of cancer nodules and inflamed surrounding thyroid tissues had numerous CD1b-, L-M2- and X-12-positive DCs suggesting that they were interdigitating cells, as well as many CD1a- and CD1c-positive DCs. Neoplastic cells of papillary carcinomas were more frequently reactive with antibodies against IL-1 alpha and TNF-alpha than those of follicular carcinomas, and a good correlation between their immunoreactivity and the frequency of DCs was found. These data suggest that cytokines such as IL-1 alpha and TNF-alpha released from carcinoma cells and cells in the cancer stroma may regulate the infiltration and maturation of dendritic/Langerhans cells, and that this process may be better preserved in papillary than in follicular carcinomas.
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PMID:Immunohistochemical analysis of dendritic/Langerhans cells in thyroid carcinomas. 757 48

The present paper deals with more precise characterization of Langerhans cells (LC) and accompanying lymphocytes in lung LC histiocytosis (LCH) and primary lung peripheral adenocarcinomas using immunohistochemical methods with various kinds of monoclonal antibodies against cell adhesion and activation markers and some cytokines. Tissue specimens were obtained from 4 patients with pulmonary LCH and from 29 patients with primary lung peripheral adenocarcinoma. In florid (exudative and granulomatous) nonfibrotic LCH lesions, LC, particularly those in contact with lymphocytes, were S100, CD1a, MHC Class II, CD11a and c, CD16, and CD54 positive. In this context, LC were CD4+ and CD25+. Lymphocytes around LC were CD3+ with a "memory" phenotype (CD45RO+) and, frequently, CD25+ and HLA-DR+. S100+ and CD1a+ LC were commonly observed in adenocarcinomas subclassified as papillary and as nonmucinous bronchioloalveolar, in both cases mainly where Clara cells and Type II pneumocytes were present. In carcinomas the vast majority of LC were HLA-DR+ and, rarely, weakly CD16+, CD25+, and CD54+. The infiltration of reactive cells in cancer tissue was mainly represented by T lymphocytes (CD3+CD45RO+). These T cells were HLA-DR- and CD25-. The presence of LC was associated with a strong reactivity of epithelial cells with antibodies PE-10 and 439-9B, both recognizing molecules mainly expressed by Type II alveolar cells. Several cells in LCH florid lesions showed immunoreactivity for both IL-1 alpha and beta. Immunostaining for IFN-gamma revealed the presence in the same areas of some positive cells showing lymphoid morphology. No IL-1 or IFN-gamma reactivity was found in adenocarcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Langerhans cells in Langerhans cell histiocytosis and peripheral adenocarcinomas of the lung. 769 Feb 10

To date no hematopoietic progenitors of dendritic Langerhans' cells (DLC), which represent an highly efficient class of antigen presenting cells, have been identified or the cytokines they elaborate have been defined. Here we describe an acute leukemia patient whose blasts (90-96% in peripheral blood and bone marrow) had a phenotype consistent with putative progenitors of DLC. The patient was treated with ara-C and VP-16 but did not achieve remission. The blasts had lobulated nuclei, no cytoplasmic vacuolation or Auer rods and were weakly positive for acid phosphatase and non-specific esterase and negative for PAS, granzyme A, dipeptidyl aminopeptidase IV, ATPase/ADPase and lysozyme production. The blasts were positive for CD1a, CD4, CD16, CD35, HLADR, HLADQ, CD11b, CD11c, CD14, CD33, CD34, CD11a, CD71, CD19, CD25, IL-2R beta and negative for CD2, CD7, CD8, CD10, CD22, CD56, CD57, surface or cytoplasmic CD3, TCR delta and TCR beta, HTLV-1p19 and P-glycoprotein. On liquid culture with or without 5 x 10(-9) M 12-O-tetradecanoylphorbol-13-acetate (TPA) for 3 days, the blasts formed aggregates of proliferating and elongating cells on the wall of the flasks with a decline in CD34, numerous dendritic processes appeared on the cells and there was strong positivity for ATPase/ADPase, but no other changes in phenotype. No macrophages were observed, indicating derivation from separate DLCs. Cytogenetic analysis showed chromosomal abnormalities and electron microscopy showed Birbeck granules. Southern blotting of DNA showed rearrangement of one allele for both JH and TCR beta but no HTLV-1 related sequences. Culture supernatants from blasts cultured with or without TPA showed the production of large amounts of IL-8, IL-6, TNF-alpha, MIP-1 alpha, IL-10 and interferon gamma and modest amounts of IL-1 alpha, GM-CSF and stem cell factor. The presence not only of CD1a, HLADR, HLADQ and many other characteristics including Birbeck granules, but also differentiation along the lines of DLC with appearance of dendritic processes on the cells and expression of ATPase/ADPase activity, indicate that the leukemic blasts in our patient represented a leukemic counterpart of normal progenitors of DLC and the leukemia a new entity which could possibly be classified as AML-M8. Lastly, many pro-inflammatory cytokines produced by DLC could contribute to inflammation and IL-10 to immunosuppression.
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PMID:Phenotype, genotype and cytokine production in acute leukemia involving progenitors of dendritic Langerhans' cells. 791 55