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Involvement of CD252 (CD134L) and IL-2 in the Expression of Cytotoxic Proteins in Bacterial- or Viral-Activated Human T Cells¹

Michael Walch^2,*, Silvana K. Rampini, Isabelle Stoeckli^*,||, Sonja Latinovic-Golic^*, Claudia Dumrese^*,||, Hanna Sundstrom^*, Alexander Vogetseder^*, Joseph Marino^*, Daniel L. Glauser, Maries van den Broek, Peter Sander^,¶, Peter Groscurth^* and Urs Ziegler^3,*,||

^* Division of Cell Biology, Institute of Anatomy, Institute of Medical Microbiology, Institute of Virology, and Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland; ^¶ National Center for Mycobacteria, Zurich, Switzerland; and ^|| Center for Microsocopy and Image Analysis, Zurich, Switzerland

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- and TNF- 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Kurt and Senta Herrmann-Foundation and in part by the Swiss National Science Foundation (3200-068488; 3100AO_120326) to P.S. S.R is supported by grants from Swiss Lung Foundation and Wolfermann-Naegeli-Foundation. M.W. is supported by a fellowship from the Stiefel- Zangger-Foundation.

² Current address: Immune Disease Institute, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115.

³ Address correspondence and reprint requests to Dr. Urs Ziegler, Center for Microsocopy and Image Analysis, Winterthurerstrasse 190, 8057 Zurich, Switzerland. E-mail address: ziegler{at}zmb.uzh.ch

⁴ Abbreviations used in this paper: LCMV, lymphocytic choriomeningitis virus; aLDC, autologous lymphocyte-dendritic cell; DC, dendritic cell; MOI, multiplicity of infection.