Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06126 (CD1a)
2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dendritic cells (DC), the most potent antigen-presenting cells found to date, can be generated from the adherent fraction of peripheral blood mononuclear cells (PBMC) by culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. When interferon gamma (IFN-gamma) was added to the culture medium, the expression of CD1a, CD4 and CD80 markers were significantly reduced, while that of HLA-A, B, C, MHC II (MHC-DR), CD11a and CD54 were increased. T cell proliferation analysis showed that the DC derived from monocytes cultured with GM-CSF, IL-4 and IFN-gamma only induced weak responses in both activated and naive allogenic CD4(+) and CD8(+) T cells when compared to the reaction elicited by DC cultured without IFN-gamma. Furthermore, the DC derived from cultures with IFN-gamma, loaded with an immunogenic peptide derived from the HER2/neu protein [HER2 (9466)], only induced low levels of TNF release and weak proliferative responses in a specific cytotoxic CD8(+) T lymphocyte clone. Therefore, our results indicate that IFN-gamma negatively influences the differentiation and function of monocyte-derived DC by affecting the expression of surface molecules involved in their antigen-presenting function. This supports the general hypothesis that there exists a feedback immune regulatory mechanism between T cells and monocytes/DC.
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PMID:Interferon gamma impairs the ability of monocyte-derived dendritic cells to present tumour-specific and allo-specific antigens and reduces their expression of CD1A, CD80 AND CD4. 981 27

Many strategies have been proposed to circumvent cancer development or prevent its growth. One of the promising strategies is to direct the immune response toward tumour antigens. This can be achieved by loading dendritic cells, the most potent antigen presenting cells, with tumour antigens. Fusion of dendritic cells (DC) with tumour cells is an attractive way to load the DC with all tumour antigens regardless of their immunogenicity status and the fact that they have, or not, been identified. The aim of our study was to characterise the immunophenotype of fused cells, monitor the evolution of the fusion interface and the distribution of surface antigens over time and assess for their maturation status and functionality in vitro. We used polyethylene glycol to fuse DC with Her2/neu positive breast cancer cell line T-47D. We demonstrate that false positive events accounted in flow cytometry can be identified using confocal microscopy to avoid an overestimation of fusion efficiency and to distinguish clearly hybrid cells from aggregated or phagocytosed cells. We used imaging means to demonstrate the conservation of presentation molecules (MHC II, CD1a), co-stimulatory molecules (CD40, CD80, CD86), as well as tumour antigens (Her2/neu, cytokeratins) in optimised conditions. Fused cells were only recognisable for 48 h as assessed by membrane staining and membranous antigen distribution. Fusion was necessary for their maturation to be accompanied by functional activity such as secretion of cytokines and perforin. These results suggest that hybrid cells generated by the fusion of DC and tumour cells can be easily identified and characterised using imaging techniques, and that, regarding functionality and cytokine secretion, they appear to be good candidates for anti-tumour therapies namely in breast cancer.
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PMID:Characteristics of hybrid cells obtained by dendritic cell/tumour cell fusion in a T-47D breast cancer cell line model indicate their potential as anti-tumour vaccines. 1798 63