Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A wide variety of human tumors express IL-10 for reasons poorly understood. We have analyzed the effect of spontaneous IL-10 expression by a mouse tumor (J558L) on its immunoparalyzing effect. Because "cross-priming" of T cells by host Ag-presenting cells for MHC class I-restricted tumor Ags is a major pathway for induction of tumor immunity and that is enhanced by granulocyte-macrophage (GM) CSF, we expressed this cytokine in J558L cells. GM-CSF-secreting cells were not effective when used for immunization against challenge with the parental tumor. Inhibition of IL-10 expression through an IL-10 antisense retrovirus restored the vaccine efficacy of GM-CSF-producing J558L cells, demonstrating a direct role of IL-10 in paralyzing the GM-CSF-induced antitumor immune response. Since the tumor used for challenge produced IL-10, we conclude that IL-10 interfered primarily with the initiation but not the effector phase of the immune response. Immunohistochemical analysis of the vaccine site showed a GM-CSF-induced accumulation of dendritic cells (DC) (MHC class II+ and DEC-205+) in the absence of IL-10. In the presence of IL-10, DC accumulation was completely inhibited. Together, our results demonstrate an antagonistic effect of IL-10 with respect to GM-CSF-induced DC accumulation and tumor immunity and suggest a new mechanism by which tumors escape immune recognition: namely by preventing APC from obtaining access to tumor Ags.
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PMID:Interleukin-10 prevents dendritic cell accumulation and vaccination with granulocyte-macrophage colony-stimulating factor gene-modified tumor cells. 921 94

The study of liver dendritic cells (DC) and their progenitors is restricted by the small numbers that can be isolated or propagated from normal hepatic tissue. We examined the ex vivo growth, phenotype, and function of these cells after the administration to mice of the recently cloned hemopoietic growth factor flt3 ligand (FL), which is highly effective in mobilizing stem/progenitor cells. FL treatment (10 microg/day for 10 days) resulted in a mean 14-fold increase in the absolute number of nonparenchymal cells recovered from collagenase-digested livers compared with the control value. Culture of these nonparenchymal cells in granulocyte-macrophage CSF (GM-CSF; 1000 U/ml) resulted in the early formation of proliferating cell clusters and maximal release (within 4-5 days) of markedly increased numbers of nonadherent, low buoyant density cells per liver. Maximal release of low buoyant density cells propagated from control livers was at the later time of 6 to 8 days. Cells from both sources were DEC-205+, CD11c+, MHC class II+, CD80(low) (i.e., low level of CD80), CD86(low) and CD40(low). This immature phenotype was linked to poor T cell allostimulatory activity, indicative of DC progenitors. Propagation of cells from livers of FL-treated mice in GM-CSF and IL-4 resulted in a more mature DC phenotype and function. Maturational changes were also observed following exposure of the GM-CSF-stimulated progenitors to type 1 collagen for 3 additional days. The ability of FL to boost production of large numbers of liver DC progenitors provides opportunities for the further study of these important APC in normal liver immunobiology and in immune-mediated hepatic disorders.
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PMID:In vivo administration of flt3 ligand markedly stimulates generation of dendritic cell progenitors from mouse liver. 937 22