Effects of CD40 ligation on human keratinocyte accessory function
CD40/CD40 ligand interactions are known to play a key role in the development of immune reactions, especially by enhancing the costimulatory function of professional antigen-presenting cells (APC). Little is known, however, about the role this receptor plays on occasional APC, i.e. cells that are in...
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Published in: | Archives of Dermatological Research Vol. 290; no. 6; pp. 325 - 330 |
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Berlin
Springer
01-06-1998
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Abstract | CD40/CD40 ligand interactions are known to play a key role in the development of immune reactions, especially by enhancing the costimulatory function of professional antigen-presenting cells (APC). Little is known, however, about the role this receptor plays on occasional APC, i.e. cells that are induced to express MHC class II molecules following an inflammatory process. In this study, we used CD40 ligand-transfected cells to analyze the effect of CD40 ligation on the phenotype, as well as accessory function, of human keratinocytes. We found that CD40 ligation enhanced ICAM-1 expression and did not upregulate HLA-DR, CD80 or CD86 expression on IFN-gamma-treated keratinocytes. CD40 triggering was not sufficient to generate primary allogeneic T-cell responses even in the presence of anti-CD28 monoclonal antibody (mAb). Moreover, CD40 ligation, in the presence or not of IFN-gamma, did not alter the accessory function of keratinocytes in PHA- or superantigen-induced T-cell activation. The lack of effect on the T-cell response was confirmed in blocking experiments using anti-CD40 mAbs. Collectively, these results suggest that CD40-CD40 ligand interactions on nonprofessional APC may amplify the inflammatory reaction without providing a mitogenic signal to the T cells. |
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AbstractList | CD40/CD40 ligand interactions are known to play a key role in the development of immune reactions, especially by enhancing the costimulatory function of professional antigen-presenting cells (APC). Little is known, however, about the role this receptor plays on occasional APC, i.e. cells that are induced to express MHC class II molecules following an inflammatory process. In this study, we used CD40 ligand-transfected cells to analyze the effect of CD40 ligation on the phenotype, as well as accessory function, of human keratinocytes. We found that CD40 ligation enhanced ICAM-1 expression and did not upregulate HLA-DR, CD80 or CD86 expression on IFN-gamma-treated keratinocytes. CD40 triggering was not sufficient to generate primary allogeneic T-cell responses even in the presence of anti-CD28 monoclonal antibody (mAb). Moreover, CD40 ligation, in the presence or not of IFN-gamma, did not alter the accessory function of keratinocytes in PHA- or superantigen-induced T-cell activation. The lack of effect on the T-cell response was confirmed in blocking experiments using anti-CD40 mAbs. Collectively, these results suggest that CD40-CD40 ligand interactions on nonprofessional APC may amplify the inflammatory reaction without providing a mitogenic signal to the T cells. |
Author | SCHMITT, D CONCHA, M PEGUET-NAVARRO, J GROUSSON, J |
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Keywords | Human Cell proliferation Cell culture Flow cytometry Antigen presentation Skin disease Ligand Pathogenesis Class II histocompatibility antigen Cytokine Cell adhesion molecule Inflammation In vitro Phenotype T-Lymphocyte Keratinocyte Skin Biological receptor |
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SubjectTerms | 3T3 Cells Animals Antibodies, Monoclonal - immunology Antibodies, Monoclonal - pharmacology Antiviral Agents - pharmacology Biological and medical sciences CD40 Antigens - immunology CD40 Antigens - metabolism Cell Division - drug effects Cell Division - immunology Dermatology Enterotoxins - pharmacology Humans Intercellular Adhesion Molecule-1 - biosynthesis Intercellular Adhesion Molecule-1 - drug effects Interferon-gamma - pharmacology Keratinocytes - drug effects Keratinocytes - immunology Keratinocytes - metabolism L Cells (Cell Line) Medical sciences Mice Mitogens - pharmacology Phytohemagglutinins - pharmacology Skin involvement in other diseases. Miscellaneous. General aspects Superantigens - immunology Superantigens - pharmacology T-Lymphocytes - cytology T-Lymphocytes - immunology |
Title | Effects of CD40 ligation on human keratinocyte accessory function |
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