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Characterization of human inducible costimulator ligand expression and function

Item Type:Article
Title:Characterization of human inducible costimulator ligand expression and function
Creators Name:Aicher, A. and Hayden-Ledbetter, M. and Brady, W.A. and Pezzutto, A. and Richter, G. and Magaletti, D. and Buckwalter, S. and Ledbetter, J.A. and Clark, E.A.
Abstract:The inducible costimulator (ICOS) is the newest member of the CD28/CD152 receptor family involved in regulating T cell activation. We constructed a soluble-Ig fusion protein of the extracellular domain of human ICOS and used it as a probe to characterize expression patterns of the ICOS ligand (ICOSL). ICOSIg did not bind to CD80- or CD86-transfected Chinese hamster ovary cell lines, demonstrating that ICOSL is distinct from those ligands identified for CD28/CD152. ICOSIg showed selective binding to monocytic and B cell lines, whereas binding was undetectable on unstimulated monocytes and peripheral blood T and B cells. Expression of ICOSL was induced on monocytes after integrin-dependent plastic adhesion. Pretreatment of monocytes with mAb to the {beta}2-integrin subunit CD18 decreased adhesion and abolished ICOSL up-regulation but had no effect on CD80/86 (CD152 ligand (CD152L)) expression. Both ICOSL and CD152L were up-regulated on monocytes by IFN-{gamma} but by distinct signaling pathways. Unlike CD152L expression, ICOSL expression did not change when monocytes were differentiated into dendritic cells (DCs) or after DCs were induced to mature by LPS, TNF-{alpha}, or CD40 ligation. Addition of ICOSIg to allogeneic MLRs between DCs and T cells reduced T cell proliferative responses but did so less efficiently than CTLA4Ig (CD152Ig) did. Similarly, ICOSIg also blocked Ag-specific T cell proliferation to tetanus toxoid. Thus, ICOSL, like CD80/86, is expressed on activated monocytes and dendritic cells but is regulated differently and delivers distinct signals to T cells that can be specifically inhibited by ICOSIg.
Keywords:Abatacept, B-Lymphocytes, CD Antigens, CD14 Antigens, CD28 Antigens, CD3 Antigens, CD80 Antigens, CD86 Antigens, CD4-Positive T-Lymphocytes, Cell Line, COS Cells, CTLA-4 Antigen, Cultured Tumor Cells, Dendritic Cells, Differentiation Antigens, Immunoconjugates, Immunosuppressive Agents, Inducible T-Cell Co-Stimulator Protein, Ligands, Lymphocyte Activation, Membrane Glycoproteins, Monoclonal Antibodies, Monocytes, Protein Binding, Recombinant Fusion Proteins, Solubility, T-Lymphocyte Differentiation Antigens, T-Lymphocyte Epitopes, Animals
Source:Journal of Immunology
Publisher:American Association of Immunologists
Page Range:4689-4696
Date:1 May 2000
Official Publication:https://doi.org/10.4049/jimmunol.164.9.4689
PubMed:View item in PubMed

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