NDLI: ICOS-ligand, expressed on human endothelial cells, costimulates Th1 and Th2 cytokine secretion by memory CD4+ T cells.

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ICOS-ligand, expressed on human endothelial cells, costimulates Th1 and Th2 cytokine secretion by memory CD4+ T cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Büchner, Kerstin Khayyamian, Saman Henn, Volker Hutloff, Andreas Mages, Hans W. Kroczek, Richard A. Gräfe, Michael
Description	Author Affiliation: Khayyamian S ( Molecular Immunology, Robert Koch-Institute, Nordufer 20, D-13353 Berlin, Germany.);
Abstract	Endothelial cells (EC) play a central role in inflammatory immune responses and efficiently induce effector functions in T cells, despite lacking the classical costimulatory ligands CD80 and CD86. By using the mAb HIL-131 we now demonstrate that human inducible costimulator-ligand (ICOS-L), a molecule related to CD80/CD86, is constitutively expressed on human EC in vivo. In vitro, ICOS-L expression was strongly enhanced on human umbilical vein EC and microvascular EC by the inflammatory cytokines tumor necrosis factor alpha and IL-1beta, and to a lower extent by stimulation of EC by CD40 or lipopolysaccharide. Coculture of MHC class II(+) EC with resting memory CD4(+) T cells in the presence of superantigen led to a marked up-regulation of ICOS on T cells and to the production of Th1 (IFN-gamma, IL-2) and Th2 cytokines (IL-4, IL-10, IL-13). When these cocultures were performed in the presence of the inhibitory mAb HIL-131, secretion of all cytokines was reduced by about 50-80%, indicating that ICOS-L is a major costimulator in EC-mediated T cell activation. Taken together, our data suggest an important physiological role of ICOS-L in the reactivation of effector/memory T cells on the endothelium controlling the entry of immune cells into inflamed tissue.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	9
Volume Number	99
Language	English
Publisher	National Academy of Sciences
Publisher Date	2002-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens, Differentiation, T-Lymphocyte Biosynthesis Physiology CD4-Positive T-Lymphocytes Metabolism Endothelium, Vascular Cytology Protein Biosynthesis Proteins Th1 Cells Th2 Cells Alternative Splicing Animals Antibodies, Monoclonal Antigens, CD Antigens, CD80 Antigens, CD86 Cell Division Cells, Cultured Cytokines Flow Cytometry Inducible T-Cell Co-Stimulator Ligand Inducible T-Cell Co-Stimulator Protein Interferon-gamma Interleukin-1 Interleukin-10 Interleukin-13 Interleukin-2 Interleukin-4 Ligands Lipopolysaccharides Membrane Glycoproteins Mice Mice, Inbred BALB C Precipitin Tests Protein Binding Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes Time Factors Tumor Necrosis Factor-alpha Up-Regulation Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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