The ICOS-ligand B7-H2, expressed on human type II alveolar epithelial cells, plays a role in the pulmonary host defense system
| Autor: | Xuesong Qian, Takuma Hayashi, Yoh-ichi Tagawa, Kazunaga Agematsu, Gordon J. Freeman, Kazuo Sugane |
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| Rok vydání: | 2006 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte CD4-Positive T-Lymphocytes CD3 Complex medicine.medical_treatment T cell CD40 Ligand Immunoblotting Immunology Gene Expression Electrophoretic Mobility Shift Assay Respiratory Mucosa Ligands Inducible T-Cell Co-Stimulator Protein Inducible T-Cell Co-Stimulator Ligand Interferon-gamma Mice Antigens CD medicine Animals Humans Immunology and Allergy RNA Messenger CD154 Cell Proliferation A549 cell CD40 Innate immune system biology Reverse Transcriptase Polymerase Chain Reaction Proteins T helper cell respiratory system Coculture Techniques Cell biology Pulmonary Alveoli ICOS LIGAND Cytokine medicine.anatomical_structure biology.protein Cytokines |
| Zdroj: | European Journal of Immunology. 36:906-918 |
| ISSN: | 1521-4141 0014-2980 |
| Popis: | The mechanism of immune defense against pathogens in the lung, has so far been poorly understood. Here, we show that human type II alveolar epithelial cells play a key role in defense via interactions between B7 homolog (B7h), also known as ICOS ligand, and its receptor ICOS expressed on activated T cells. The A549 alveolar type II cell line abundantly expresses B7-H2, CD40 and B7-1, but not B7-2 or hGL50. TNF-alpha significantly induced B7-H2 and CD40 expression by A549 cells, but had no effect on B7-1 or B7-2 expression. TNF-alpha-deficient mice exhibited low B7-H2 expression on alveolar epithelial cells in comparison with wild-type mice. Co-culture of TNF-alpha pre-stimulated A549 cells with CD4+ T cells promoted CD154 expression, CD4+ T cell proliferation and cytokine production, especially IFN-gamma. Monocyte-derived TNF-alpha in combination with IFN-gamma and LPS markedly induced B7-H2 expression in A549 cells. This study thus identifies a unique costimulatory pathway via alveolar epithelial type II cells that preferentially affects T helper cell function, implying that alveolar epithelial type II cells play a crucial role in innate immunity in the lung by regulating IFN-gamma-synthesis via B7-H2/ICOS interactions. |
| Databáze: | OpenAIRE |
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