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
Main Authors: GROUSSON, J, CONCHA, M, SCHMITT, D, PEGUET-NAVARRO, J
Format: Journal Article
Language:English
Published: 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.
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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Issue 6
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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