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Characterization of human inducible costimulator ligand expression and function.
A Aicher1, M Hayden-Ledbetter, W A Brady
1Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|April 26, 2000
Summary
The inducible costimulator ligand (ICOSL) is expressed on activated monocytes and dendritic cells, distinct from CD28/CD152 ligands. ICOSL expression is regulated differently and impacts T cell activation, as shown by ICOSIg blocking studies.
Area of Science:
- Immunology
- Cell Biology
Background:
- The inducible costimulator (ICOS) is a key regulator of T cell activation within the CD28/CD152 receptor family.
- Understanding the expression and function of ICOS ligand (ICOSL) is crucial for deciphering T cell-mediated immune responses.
Purpose of the Study:
- To characterize the expression patterns of ICOSL using a soluble-Ig fusion protein (ICOSIg).
- To determine if ICOSL is distinct from known ligands for CD28/CD152 (CD80/CD86).
- To investigate the regulation and functional impact of ICOSL on T cell activation.
Main Methods:
- Construction of a soluble human ICOS-Ig fusion protein (ICOSIg) as a molecular probe.
- Assessment of ICOSIg binding to various cell lines, including monocytic, B cell, and T cell lines.
- Induction of ICOSL expression on monocytes via integrin-dependent adhesion and IFN-gamma stimulation.
- Comparison of ICOSL regulation with CD80/86 (CD152 ligand) expression.
- Evaluation of ICOSL expression during monocyte differentiation into dendritic cells (DCs) and DC maturation.
- Inhibition studies using ICOSIg and CTLA4Ig (CD152Ig) in allogeneic mixed lymphocyte reactions (MLRs) and antigen-specific T cell proliferation assays.
Main Results:
- ICOSIg demonstrated selective binding to monocytic and B cell lines, confirming ICOSL is distinct from CD80/CD86.
- ICOSL expression was induced on monocytes upon adhesion and by IFN-gamma, via distinct pathways from CD80/CD86.
- ICOSL expression remained stable during monocyte-to-dendritic cell differentiation and DC maturation.
- ICOSIg partially inhibited T cell proliferation in MLRs and antigen-specific responses, though less effectively than CTLA4Ig.
Conclusions:
- ICOSL is expressed on activated monocytes and dendritic cells, with unique regulatory mechanisms compared to CD80/CD86.
- ICOSL delivers distinct signals to T cells that can be specifically inhibited by ICOSIg.
- These findings highlight ICOSL as a novel target for modulating T cell responses in immune-related conditions.