title: Involvement of CD252 (CD134L) and IL-2 in the expression of cytotoxic proteins in bacterial- or viral-activated human T cells.
abstract: Regulation of cytotoxic effector molecule expression in human CTLs after viral or bacterial activation is poorly understood. By using human autologous dendritic cells (DCs) to prime T lymphocytes, we found perforin only highly up-regulated in virus- (HSV-1, vaccinia virus) but not in intracellular bacteria- (Listeria innocua, Listeria monocytogenes, Mycobacterium tuberculosis, Chlamydophila pneumoniae) activated CTLs. In contrast, larger quantities of IFN-gamma and TNF-alpha were produced in Listeria-stimulated cultures. Granzyme B and granulysin were similarly up-regulated by all tested viruses and intracellular bacteria. DCs infected with HSV-1 showed enhanced surface expression of the costimulatory molecule CD252 (CD134L) compared with Listeria-infected DC and induced enhanced secretion of IL-2. Adding blocking CD134 or neutralizing IL-2 Abs during T cell activation reduced the HSV-dependent up-regulation of perforin. These data indicate a distinct CTL effector function in response to intracellular pathogens triggered via differing endogenous IL-2 production upon costimulation through CD252.
authors.affiliation: Division of Cell Biology, Institute of Anatomy, University of Zurich, Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Walch
authors.forename: Silvana K
authors.initials: SK
authors.lastname: Rampini
authors.forename: Isabelle
authors.initials: I
authors.lastname: Stoeckli
authors.forename: Sonja
authors.initials: S
authors.lastname: Latinovic-Golic
authors.forename: Claudia
authors.initials: C
authors.lastname: Dumrese
authors.forename: Hanna
authors.initials: H
authors.lastname: Sundstrom
authors.forename: Alexander
authors.initials: A
authors.lastname: Vogetseder
authors.forename: Joseph
authors.initials: J
authors.lastname: Marino
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Glauser
authors.forename: Maries
authors.initials: M
authors.lastname: van den Broek
authors.forename: Peter
authors.initials: P
authors.lastname: Sander
authors.forename: Peter
authors.initials: P
authors.lastname: Groscurth
authors.forename: Urs
authors.initials: U
authors.lastname: Ziegler
mesh_terms: D002478:Cells, Cultured; D023501:Chlamydophila / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D008087:Listeria / Q000276:immunology / Q000472:pathogenicity; D008213:Lymphocyte Activation / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D053278:OX40 Ligand / Q000276:immunology*; D054353:Perforin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D015854:Up-Regulation / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology
chemical_list: D007376:Interleukin-2; D053278:OX40 Ligand; C089251:TNFSF4 protein, human; D054353:Perforin