ps1145 and Neoplasms

Human T cells expressing γδ T cell receptor have a potential to show antigen-presenting cell-like phenotype and function upon their activation. However, the mechanisms that underlie the alterations in human γδ T cells remain largely unclear. In this study, we have investigated the molecular characteristics of human γδ T cells related to their acquisition of antigen-presenting capacity in comparison with activated αβ T cells. We found that activated γδ but not αβ T cells upregulated cell surface expression of a scavenger receptor, CD36, which seemed to be mediated by signaling through mitogen-activated protein kinase and/or NF-κB pathways. Confocal microscopical analysis revealed that activated γδ T cells can phagocytose protein antigens. Activated γδ T cells could induce tumor antigen-specific CD8(+) T cells using both apoptotic and live tumor cells as antigen resources. Furthermore, we detected that C/EBPα, a critical transcription factor for the development of myeloid-lineage cells, is expressed much higher in γδ T cells than in αβ T cells. These results unveiled the molecular mechanisms for the elicitation of antigen-presenting functions in γδ T cells and would also help designing new approaches for γδ T cell-mediated human cancer immunotherapy.

Topics: Antigen Presentation; Antigens, Neoplasm; CCAAT-Enhancer-Binding Proteins; CD36 Antigens; CD8-Positive T-Lymphocytes; Cell Differentiation; Cell Line, Tumor; Cell Lineage; Cytotoxicity, Immunologic; Heterocyclic Compounds, 3-Ring; Humans; Imidazoles; Immunotherapy; Lymphocyte Activation; MART-1 Antigen; Myeloid Cells; Neoplasms; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phagocytosis; Pyridines; Receptors, Antigen, T-Cell, gamma-delta; Signal Transduction; T-Lymphocytes; Up-Regulation