Human Tumor Antigen MUC1 Is Chemotactic for Immature Dendritic Cells and Elicits Maturation but Does Not Promote Th1 Type Immunity
| Autor: | O. M. Zack Howard, Hui Fang Dong, Franz-Georg Hanisch, Joost J. Oppenheim, Olivera J. Finn, Casey A. Carlos |
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| Rok vydání: | 2005 |
| Předmět: |
Protein Conformation
Cellular differentiation T cell Molecular Sequence Data Immunology chemical and pharmacologic phenomena Lymphocyte Activation Immune system Antigen Biomarkers Tumor medicine Humans Protein Isoforms Immunology and Allergy Amino Acid Sequence Cells Cultured CD86 Immunity Cellular CD40 Follicular dendritic cells biology Cell Membrane Mucin-1 Cell Differentiation hemic and immune systems Dendritic Cells Th1 Cells Coculture Techniques Peptide Fragments Cell biology Chemotaxis Leukocyte medicine.anatomical_structure Sialic Acids biology.protein CD80 |
| Zdroj: | The Journal of Immunology. 175:1628-1635 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | The immunostimulatory outcome of the interactions of many pathogens with dendritic cells (DCs) has been well characterized. There are many fewer examples of similar interactions between DCs and self-molecules, especially the abnormal self-proteins such as many tumor Ags, and their effects on DC function and the immune response. We show that human epithelial cell Ag MUC1 mucin is recognized in its aberrantly glycosylated form on tumor cells by immature human myeloid DCs as both a chemoattractant (through its polypeptide core) and a maturation and activation signal (through its carbohydrate moieties). On encounter with MUC1, similar to the encounter with LPS, immature DCs increase cell surface expression of CD80, CD86, CD40, and CD83 molecules and the production of IL-6 and TNF-α cytokines but fail to make IL-12. When these DCs are cocultured with allogeneic CD4+ T cells, they induce production of IL-13 and IL-5 and lower levels of IL-2, thus failing to induce a type 1 response. Our data suggest that, in vivo in cancer patients, MUC1 attracts immature DCs to the tumor through chemotaxis and subverts their function by negatively affecting their ability to stimulate type 1 helper T cell responses important for tumor rejection. |
| Databáze: | OpenAIRE |
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