title: [Towards novel tuberculosis and leprosy vaccine development: the role of Th1-inducing peptide in cytotoxic T cell differentiation].
abstract: The effectiveness of a vaccine against tuberculosis and leprosy is mainly judged by its capability to induce memory CD8 cytotoxic T cells (CTL). It has been reported that 'help' from CD4+ T cells is required to induce memory CTL. However, how CD4+ T cells instruct or support memory CTL during priming phase has not been resolved in detail. Therefore, we examined the helper function of CD4+ T cells in CTL differentiation. Peptide-25 is the major T cell epitope of Ag85B of Mycobacterium tuberculosis. We found that this peptide induced the expression of T-bet and TATA box binding protein-associated factor that can induce the chromatin remodeling of ifn-gamma gene, and as a result induced Th1 differentiation even in the absence of IFN-gamma and IL-12. Next, we established an in vitro CTL differentiation system using Peptide-25, Peptide-25 specific CD4+ T cells, OVA specific CD8+ T cells and splenic DC. By using this system, we found that CD4+ T cells activated DC even in the absence of IFN-gamma and CD40 ligand association, and the activated DC induced the functional differentiation of CTL. To identify the regulatory factors for DC activation, we analyzed the gene expression profile of helper CD4 T cells and identified 27 genes. Taken together, these results suggest that the inducing factors for Th1 differentiation are not indispensable to induce the functional differentiation of CTL.
authors.affiliation: Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases. toshikit@niid.go.jp
authors.forename: Toshiki
authors.initials: T
authors.lastname: Tamura
authors.affiliation: Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shimohakamada
authors.affiliation: Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Makino
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D042002:Chromatin Assembly and Disassembly; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D007918:Leprosy / Q000517:prevention & control*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000276:immunology*; D020825:T-Box Domain Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D035181:TATA-Box Binding Protein; D018417:Th1 Cells / Q000276:immunology*; D014376:Tuberculosis / Q000517:prevention & control*; D000098815:T-bet Transcription Factor
chemical_list: D018984:Epitopes, T-Lymphocyte; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D035181:TATA-Box Binding Protein; D007371:Interferon-gamma