Involvement of CD252 (CD134L) and IL-2 in the Expression of Cytotoxic Proteins in Bacterial- or Viral-Activated Human T Cells

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 b...

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Published in:The Journal of immunology (1950) 2009-06, Vol.182 (12), p.7569-7579
Main Authors: Walch, Michael, Rampini, Silvana K, Stoeckli, Isabelle, Latinovic-Golic, Sonja, Dumrese, Claudia, Sundstrom, Hanna, Vogetseder, Alexander, Marino, Joseph, Glauser, Daniel L, van den Broek, Maries, Sander, Peter, Groscurth, Peter, Ziegler, Urs
Format: Article
Language:English
Subjects:
Cells, Cultured
Chlamydophila - immunology
Cytotoxicity, Immunologic - immunology
Dendritic Cells - immunology
Herpesvirus 1, Human - immunology
Herpesvirus 1, Human - pathogenicity
Humans
Interleukin-2 - immunology
Interleukin-2 - secretion
Listeria - immunology
Listeria - pathogenicity
Lymphocyte Activation - immunology
Mycobacterium tuberculosis - immunology
OX40 Ligand - immunology
Perforin - immunology
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
T-Lymphocytes - secretion
Transcription, Genetic - genetics
Up-Regulation - immunology
Vaccinia virus - immunology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.0800296