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)

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) specialized to internalize, process, and present antigen. They have the capacity to stimulate the primary immune response of resting T-cells. We generated DCs from the adherent cell fraction of peripheral blood, as well as from purified CD34+ cells from CML patients. Characterizing DCs from ten CML patients by flow cytometry, we found that these cells are highly positive for HLA-DR, CD1a, CD23, and CD80 and negative for CD14, CD15, and CD16. The yield of DCs ranged from 19.5 to 68%. In addition, we used a functional test of FITC-dextran uptake to verify that early DCs take up large particles (0.5-3 microm) by macropinocytosis while monocytes do not. FITC-dextran uptake was detected by flow cytometry, showing that DCs had accumulated these fluorescent particles. Electron-microscopic analysis showed no major morphological differences between normal and CML-derived DCs. Furthermore, cultured DCs were isolated by FAC sorting for CD1a and HLA-DR expression. In these highly purified cells the Ph chromosome was detected by interphase fluorescence in situ hybridization (FISH) and by fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms (FICTION); 30-85% of DCs generated were Ph-chromosome positive. It might therefore be possible not only to prime T-cells with bcr/abl-specific synthetic peptides, but also to stimulate T-cells directly with Ph-positive DCs. Use of DCs might serve as a novel therapeutic approach in CML patients, due to their ability to induce highly specific T-cell responses in an autologous system.
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PMID:Generation of dendritic cells from patients with chronic myelogenous leukemia. 1034 49

We report a method to generate dendritic cells (DC) from frozen leukapheresis products of patients with chronic myeloid leukemia (CML), using sterile culture bags and serum-free culture medium, ie conditions feasible for re-infusion into the patient as part of immunotherapeutic protocols. Leukapheresis products were stored from harvests performed either at diagnosis (13 patients) or after chemotherapy with subsequent granulocyte colony stimulating factor (G-CSF) administration (9 patients), for Peripheral Blood Stem Cell (PBSC) collections. In the presence of optimal concentrations of GM-CSF (50 ng/ml) and IL-4 (40 ng/ml) CML progenitors differentiated on day 7 and 14 of culture to DC, expressing CD1a,HLA-DR and CD86 surface antigens. Mature DCs exhibited on average 12-fold higher allo-stimulatory capacity for CD4+ and CD8+ cells compared to non-cultured PBMC in mixed lymphocyte reaction (MLR). Only DCs obtained from CML patients at diagnosis exhibited bcr/abl fusion gene when tested by fluorescent in situ hybridization (FISH). CD34-selection on leukapheresis products from diagnosis (7 patients) resulted in later maturation of DCs (after 14-15 d), compared to the nonselected PBMC. CD34-selection significantly increased the DC growth, and improved the allo-stimulatory capacity in MLR (on average on day 14, 3.5- and 2.3-fold, respectively). Large differences were observed between individual patients and different leukapheresis products from the same patient. Our report demonstrates the possibility to generate ex vivo autologous functionally active DC in CML in a way that allows their clinical application as immunotherapeutic agents.
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PMID:Generation of dendritic cells from peripheral blood of patients at different stages of chronic myeloid leukemia. 1111 5

Chronic myelogenous leukemia is caused by the acquisition of the reciprocal (9;22)(q34;q11) chromosomal translocation in hematopoietic stem cells. The fusion protein showed higher and aberrant tyrosine kinase activity. The inhibition of the tyrosine kinase activity of the protein represents a specific therapeutic strategy for bcr/abl-expressing leukemias. STI571 is a compound of the 2-phenylaminopyrimidine class that selectively inhibits the tyrosine kinase activity of the Abl protein tyrosine kinase. In this study, we evaluated the effects of STI571 on antigen presentation of dendritic cells generated from the patients with CML. The data showed that by the addition of STI571 the dendritic cells derived from CML clone showed an increased expression of CD1a, CD83, CD80 and CD86 by flow cytometry analysis and showed more intense abilities of allogeneic antigen presentation by mixed leukocyte culture, compared with the control cells without STI571. Our results suggested that STI571 not only has a direct cytotoxic effect on bcr-abl gene rearranged cells but also an indirect effect associated with increased anti-leukemic immunological function due to an intensified antigen presentation.
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PMID:The effects of STI571 on antigen presentation of dendritic cells generated from patients with chronic myelogenous leukemia. 1280 11