RRC ID 1987
Author Kubota K.
Title A novel functional T cell hybridoma recognizes macrophage cell death induced by bacteria: a possible role for innate lymphocytes in bacterial infection.
Journal J. Immunol.
Abstract We have established a novel TCRalphabeta (TCRVbeta6)(+)CD4(-)CD8(-) T cell hybridoma designated B6HO3. When the B6HO3 cells were cocultured with bacterial-infected J774 macrophage-like cells, IFN-gamma production by B6HO3 cells was triggered through direct cell-cell contact with dying J774 cells infected with Listeria monocytogenes (LM), Shigella flexneri, or Salmonella typhimurium that expressed the type III secretion system, but not with intact J774 cells infected with heat-killed LM, nonhemolytic lysteriolysin O-deficient (Hly(-)) LM, plasmid-cured Shigella, or stationary-phase Salmonella. However, the triggering of B6HO3 cells for IFN-gamma production involved neither dying hepatoma cells infected with LM nor dying J774 cells caused by gliotoxin treatment or freeze thawing. Cycloheximide and Abs to H-2K(d), H-2D(d), Ia(d), CD1d, TCRVbeta6, and IL-12 did not inhibit the contact-dependent IFN-gamma response, indicating that this IFN-gamma response did not require de novo protein synthesis in bacterial-infected J774 cells and was TCR and IL-12 independent. Thus, in an as yet undefined way, B6HO3 hybridoma recognizes a specialized form of macrophage cell death resulting from bacterial infection and consequently produces IFN-gamma. Moreover, contact-dependent interaction of minor subsets of splenic alphabeta T cells, including NKT cells with dying LM-infected J774 and bone marrow-derived macrophage (BMM) cells, proved to provide an IFN-gamma-productive stimulus for these minor T cell populations, to which the parental T cell of the B6HO3 hybridoma appeared to belong. Unexpectedly, subsets of gammadelta T and NK cells similarly responded to dying LM-infected macrophage cells. These results propose that innate lymphocytes may possess a recognition system sensing macrophage cell "danger" resulting from bacterial infection.
Volume 176(12)
Pages 7576-88
Published 2006-6-15
DOI 10.4049/jimmunol.176.12.7576
PII 176/12/7576
PMID 16751404
MeSH Animals Antibody-Dependent Cell Cytotoxicity / immunology* Carcinoma, Hepatocellular / microbiology Carcinoma, Hepatocellular / pathology Cell Communication / immunology Cell Death / immunology Cell Line, Tumor Coculture Techniques Cross-Linking Reagents / metabolism Cross-Priming / immunology Freezing Gliotoxin / immunology Hybridomas Immunophenotyping Interferon-gamma / biosynthesis Listeriosis / immunology Listeriosis / microbiology Lymphoma, T-Cell / immunology Lymphoma, T-Cell / microbiology Lymphoma, T-Cell / pathology Macrophages / immunology* Macrophages / microbiology* Macrophages / pathology Mice Mice, Inbred C3H Mice, Inbred C57BL Mice, Inbred DBA Receptor-CD3 Complex, Antigen, T-Cell / immunology Receptor-CD3 Complex, Antigen, T-Cell / metabolism Receptors, Antigen, T-Cell, alpha-beta / immunology Receptors, Antigen, T-Cell, alpha-beta / metabolism Receptors, Antigen, T-Cell, gamma-delta / immunology Receptors, Antigen, T-Cell, gamma-delta / metabolism T-Lymphocyte Subsets / immunology* T-Lymphocyte Subsets / metabolism T-Lymphocyte Subsets / microbiology*
IF 4.718
Times Cited 8
Human and Animal Cells Hepa 1-6