title: H2-M3-restricted CD8+ T cells augment CD4+ T-cell responses by promoting DC maturation.
abstract: Infection with Listeria monocytogenes triggers the activation and expansion of nonconventional CD8+ T cells restricted by the MHC class Ib molecule, H2-M3. H2-M3-restricted CD8+ T cells exhibit a memory phenotype, rapidly produce cytokines, and reach peak frequencies sooner than conventional MHC class Ia-restricted CD8+ T cells. In this study, we found that simultaneous in vivo priming of H2-M3-restricted T cells and adoptively transferred OT-II CD4+ T cells on the same DC enhances the survival of OT-II cells. Stimulation of H2-M3-restricted T cells were found to induce DC maturation resulting in costimulatory molecule upregulation and production of TH1-type cytokines, which was dependent on both cell-to-cell contact and soluble factors, particularly TNF-alpha, produced by activated H2-M3-restricted T cells. Interestingly, H2-M3-restricted T cells were more efficient than activated NK cells in inducing DC maturation. Furthermore, we found that OVA(323-339)-coated DC matured by coculturing with peptide-stimulated H2-M3-restricted T cells were more efficient in stimulating the proliferation of Ag-activated OT-II cells. This study indicates that H2-M3-restricted T cells promote immune responses by CD4+ T cells by inducing DC maturation and suggests novel mechanisms for vaccine development.
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Chow
authors.forename: Hung-Sia
authors.initials: HS
authors.lastname: Teh
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D002454:Cell Differentiation; D002478:Cells, Cultured / Q000276:immunology / Q000378:metabolism; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D000939:Epitopes; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D008222:Lymphokines / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation
chemical_list: D000941:Antigens; D000939:Epitopes; C078177:H2-M3 antigen; D015395:Histocompatibility Antigens Class I; D008222:Lymphokines; C111390:OVA 323-339; D010446:Peptide Fragments; D010047:Ovalbumin