title: Myeloid molecular characteristics of human γδ T cells support their acquisition of tumor antigen-presenting capacity.
abstract: 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.
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Kita15 Nishi7, Sapporo, Hokkaido, 060-0815, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Muto
authors.forename: Muhammad
authors.initials: M
authors.lastname: Baghdadi
authors.forename: Ryuji
authors.initials: R
authors.lastname: Maekawa
authors.forename: Haruka
authors.initials: H
authors.lastname: Wada
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Seino
mesh_terms: D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019070:Cell Lineage; D003602:Cytotoxicity, Immunologic; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007167:Immunotherapy / Q000379:methods; D008213:Lymphocyte Activation; D058965:MART-1 Antigen / Q000276:immunology; D022423:Myeloid Cells / Q000276:immunology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D010587:Phagocytosis; D011725:Pyridines / Q000494:pharmacology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D000951:Antigens, Neoplasm; D022762:CCAAT-Enhancer-Binding Proteins; D018955:CD36 Antigens; C515848:CEBPA protein, human; D006575:Heterocyclic Compounds, 3-Ring; D007093:Imidazoles; D058965:MART-1 Antigen; D016328:NF-kappa B; C456319:PS1145; D011725:Pyridines; D016692:Receptors, Antigen, T-Cell, gamma-delta; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580