title: Selective expansion of perforin-positive CD8+ T cells by immature dendritic cells infected with live Bacillus Calmette-Guérin mycobacteria.
abstract: Live, but not dead Bacillus Calmette-Guérin (BCG) is partially protective against infection by Mycobacterium tuberculosis, which causes a disease with high mortality in immune compromised individuals. We have shown that uptake of BCG induces maturation of immature dendritic cells (DCs) regardless of the viability of the bacteria. Importantly, when T cells are cocultured with live BCG-infected DCs, the proportion of CD45RA(-) perforin(+) CD8+ T cells is markedly expanded markedly; however, little expansion is seen when T cells are cocultured with DCs harboring heat-killed BCG. The direct contact of T cells with live BCG-infected DCs was required for the expansion of perforin(+) CD8+ T cells. These CD8+ T cells demonstrated a high level of killing activity against BCG-infected macrophages. There was little contribution of cytokines, including IFN-gamma, TNF-alpha, and IL-12, to the expansion of CD8+ T cells by live BCG-infected DCs. We found that the interaction between BCG-infected DCs and CD8+ T cells through CD40/CD40L was crucial for the expansion and maturation of CD8+ T cells, the process of which was CD4-independent. In contrast, blocking the CD58/CD2 but not the CD40/CD40L interaction reduced production of IFN-gamma without affecting the maturation of CD8+ T cells. This indicates that the production of IFN-gamma and perforin by CD8+ T cells is mediated by distinct signals delivered from BCG-infected DCs. Thus, BCG-specific CD8+ CTL memory cells may be maintained for a long period of time in BCG-vaccinated hosts, and these cells could mature rapidly into effectors through the potent antigen-presenting function of DCs upon mycobacterial infection.
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama-cho, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Tsunetsugu-Yokota
authors.forename: Hideto
authors.initials: H
authors.lastname: Tamura
authors.forename: Mikiko
authors.initials: M
authors.lastname: Tachibana
authors.forename: Kiyoyuki
authors.initials: K
authors.lastname: Ogata
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Honda
authors.forename: Toshitada
authors.initials: T
authors.lastname: Takemori
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000382:microbiology*; D004705:Endocytosis; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000032:analysis*; D009163:Mycobacterium bovis / Q000378:metabolism; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013234:Stem Cells / Q000382:microbiology; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000276:immunology*
chemical_list: D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D023201:CD40 Ligand