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Skin Inflammation Is Not Sufficient to Break Tolerance Induced against a Novel Antigen
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| Zeitschriftentitel: | The Journal of Immunology |
|---|---|
| Personen und Körperschaften: | , , , , , , , |
| In: | The Journal of Immunology, 183, 2009, 2, S. 1133-1143 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
The American Association of Immunologists
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| Schlagwörter: |
| author_facet |
Holcmann, Martin Stoitzner, Patrizia Drobits, Barbara Luehrs, Petra Stingl, Georg Romani, Nikolaus Maurer, Dieter Sibilia, Maria Holcmann, Martin Stoitzner, Patrizia Drobits, Barbara Luehrs, Petra Stingl, Georg Romani, Nikolaus Maurer, Dieter Sibilia, Maria |
|---|---|
| author |
Holcmann, Martin Stoitzner, Patrizia Drobits, Barbara Luehrs, Petra Stingl, Georg Romani, Nikolaus Maurer, Dieter Sibilia, Maria |
| spellingShingle |
Holcmann, Martin Stoitzner, Patrizia Drobits, Barbara Luehrs, Petra Stingl, Georg Romani, Nikolaus Maurer, Dieter Sibilia, Maria The Journal of Immunology Skin Inflammation Is Not Sufficient to Break Tolerance Induced against a Novel Antigen Immunology Immunology and Allergy |
| author_sort |
holcmann, martin |
| spelling |
Holcmann, Martin Stoitzner, Patrizia Drobits, Barbara Luehrs, Petra Stingl, Georg Romani, Nikolaus Maurer, Dieter Sibilia, Maria 0022-1767 1550-6606 The American Association of Immunologists Immunology Immunology and Allergy http://dx.doi.org/10.4049/jimmunol.0713351 <jats:title>Abstract</jats:title> <jats:p>Depending on the cellular and molecular microenvironment, immune responses generated by skin-associated lymphoid tissues can lead to protective immunity against pathogens or to tolerance. In this study, we investigated immune responses to an Ag expressed de novo in adult skin under homeostatic conditions by generating transgenic mice producing the Ag Ova in a Cre-inducible manner in keratinocytes. Expression of Ova was induced in adult mice with a tamoxifen-inducible K5-CreER transgenic line. Although Ova was efficiently expressed by keratinocytes and presented by Langerhans cells after Cre-mediated transgene recombination, adult transgenic mice did not develop any obvious autoimmune disease symptoms like hair or weight loss. Ag-specific T cells were activated after Ova expression as indicated by up-regulation of CD44 and CD69. After in vitro restimulation Ova-specific T cells showed reduced IFN-γ production suggesting induction of tolerance after Ova expression in the skin. After transfer into Ova-expressing mice, naive OT-1 T cells transiently proliferated in skin-draining lymph nodes, infiltrated the skin but did not cause disease. Topical application of danger signals at the time of Ova induction did also not induce autoimmune disease. The unresponsiveness of Ag-specific T cells after induction of Ova expression could only be circumvented by simultaneous priming with CpG-matured, bone marrow-derived dendritic cells. Our data suggest that low amount of Ag expressed in the induction phase of the immune response results in tolerance even in the presence of danger signals and thereby helps to preserve homeostasis in the skin under normal and pathologic conditions.</jats:p> Skin Inflammation Is Not Sufficient to Break Tolerance Induced against a Novel Antigen The Journal of Immunology |
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10.4049/jimmunol.0713351 |
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| title |
Skin Inflammation Is Not Sufficient to Break Tolerance Induced against a Novel Antigen |
| title_unstemmed |
Skin Inflammation Is Not Sufficient to Break Tolerance Induced against a Novel Antigen |
| title_full |
Skin Inflammation Is Not Sufficient to Break Tolerance Induced against a Novel Antigen |
| title_fullStr |
Skin Inflammation Is Not Sufficient to Break Tolerance Induced against a Novel Antigen |
| title_full_unstemmed |
Skin Inflammation Is Not Sufficient to Break Tolerance Induced against a Novel Antigen |
| title_short |
Skin Inflammation Is Not Sufficient to Break Tolerance Induced against a Novel Antigen |
| title_sort |
skin inflammation is not sufficient to break tolerance induced against a novel antigen |
| topic |
Immunology Immunology and Allergy |
| url |
http://dx.doi.org/10.4049/jimmunol.0713351 |
| publishDate |
2009 |
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1133-1143 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>Depending on the cellular and molecular microenvironment, immune responses generated by skin-associated lymphoid tissues can lead to protective immunity against pathogens or to tolerance. In this study, we investigated immune responses to an Ag expressed de novo in adult skin under homeostatic conditions by generating transgenic mice producing the Ag Ova in a Cre-inducible manner in keratinocytes. Expression of Ova was induced in adult mice with a tamoxifen-inducible K5-CreER transgenic line. Although Ova was efficiently expressed by keratinocytes and presented by Langerhans cells after Cre-mediated transgene recombination, adult transgenic mice did not develop any obvious autoimmune disease symptoms like hair or weight loss. Ag-specific T cells were activated after Ova expression as indicated by up-regulation of CD44 and CD69. After in vitro restimulation Ova-specific T cells showed reduced IFN-γ production suggesting induction of tolerance after Ova expression in the skin. After transfer into Ova-expressing mice, naive OT-1 T cells transiently proliferated in skin-draining lymph nodes, infiltrated the skin but did not cause disease. Topical application of danger signals at the time of Ova induction did also not induce autoimmune disease. The unresponsiveness of Ag-specific T cells after induction of Ova expression could only be circumvented by simultaneous priming with CpG-matured, bone marrow-derived dendritic cells. Our data suggest that low amount of Ag expressed in the induction phase of the immune response results in tolerance even in the presence of danger signals and thereby helps to preserve homeostasis in the skin under normal and pathologic conditions.</jats:p> |
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| author | Holcmann, Martin, Stoitzner, Patrizia, Drobits, Barbara, Luehrs, Petra, Stingl, Georg, Romani, Nikolaus, Maurer, Dieter, Sibilia, Maria |
| author_facet | Holcmann, Martin, Stoitzner, Patrizia, Drobits, Barbara, Luehrs, Petra, Stingl, Georg, Romani, Nikolaus, Maurer, Dieter, Sibilia, Maria, Holcmann, Martin, Stoitzner, Patrizia, Drobits, Barbara, Luehrs, Petra, Stingl, Georg, Romani, Nikolaus, Maurer, Dieter, Sibilia, Maria |
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| description | <jats:title>Abstract</jats:title> <jats:p>Depending on the cellular and molecular microenvironment, immune responses generated by skin-associated lymphoid tissues can lead to protective immunity against pathogens or to tolerance. In this study, we investigated immune responses to an Ag expressed de novo in adult skin under homeostatic conditions by generating transgenic mice producing the Ag Ova in a Cre-inducible manner in keratinocytes. Expression of Ova was induced in adult mice with a tamoxifen-inducible K5-CreER transgenic line. Although Ova was efficiently expressed by keratinocytes and presented by Langerhans cells after Cre-mediated transgene recombination, adult transgenic mice did not develop any obvious autoimmune disease symptoms like hair or weight loss. Ag-specific T cells were activated after Ova expression as indicated by up-regulation of CD44 and CD69. After in vitro restimulation Ova-specific T cells showed reduced IFN-γ production suggesting induction of tolerance after Ova expression in the skin. After transfer into Ova-expressing mice, naive OT-1 T cells transiently proliferated in skin-draining lymph nodes, infiltrated the skin but did not cause disease. Topical application of danger signals at the time of Ova induction did also not induce autoimmune disease. The unresponsiveness of Ag-specific T cells after induction of Ova expression could only be circumvented by simultaneous priming with CpG-matured, bone marrow-derived dendritic cells. Our data suggest that low amount of Ag expressed in the induction phase of the immune response results in tolerance even in the presence of danger signals and thereby helps to preserve homeostasis in the skin under normal and pathologic conditions.</jats:p> |
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| spelling | Holcmann, Martin Stoitzner, Patrizia Drobits, Barbara Luehrs, Petra Stingl, Georg Romani, Nikolaus Maurer, Dieter Sibilia, Maria 0022-1767 1550-6606 The American Association of Immunologists Immunology Immunology and Allergy http://dx.doi.org/10.4049/jimmunol.0713351 <jats:title>Abstract</jats:title> <jats:p>Depending on the cellular and molecular microenvironment, immune responses generated by skin-associated lymphoid tissues can lead to protective immunity against pathogens or to tolerance. In this study, we investigated immune responses to an Ag expressed de novo in adult skin under homeostatic conditions by generating transgenic mice producing the Ag Ova in a Cre-inducible manner in keratinocytes. Expression of Ova was induced in adult mice with a tamoxifen-inducible K5-CreER transgenic line. Although Ova was efficiently expressed by keratinocytes and presented by Langerhans cells after Cre-mediated transgene recombination, adult transgenic mice did not develop any obvious autoimmune disease symptoms like hair or weight loss. Ag-specific T cells were activated after Ova expression as indicated by up-regulation of CD44 and CD69. After in vitro restimulation Ova-specific T cells showed reduced IFN-γ production suggesting induction of tolerance after Ova expression in the skin. After transfer into Ova-expressing mice, naive OT-1 T cells transiently proliferated in skin-draining lymph nodes, infiltrated the skin but did not cause disease. Topical application of danger signals at the time of Ova induction did also not induce autoimmune disease. The unresponsiveness of Ag-specific T cells after induction of Ova expression could only be circumvented by simultaneous priming with CpG-matured, bone marrow-derived dendritic cells. Our data suggest that low amount of Ag expressed in the induction phase of the immune response results in tolerance even in the presence of danger signals and thereby helps to preserve homeostasis in the skin under normal and pathologic conditions.</jats:p> Skin Inflammation Is Not Sufficient to Break Tolerance Induced against a Novel Antigen The Journal of Immunology |
| spellingShingle | Holcmann, Martin, Stoitzner, Patrizia, Drobits, Barbara, Luehrs, Petra, Stingl, Georg, Romani, Nikolaus, Maurer, Dieter, Sibilia, Maria, The Journal of Immunology, Skin Inflammation Is Not Sufficient to Break Tolerance Induced against a Novel Antigen, Immunology, Immunology and Allergy |
| title | Skin Inflammation Is Not Sufficient to Break Tolerance Induced against a Novel Antigen |
| title_full | Skin Inflammation Is Not Sufficient to Break Tolerance Induced against a Novel Antigen |
| title_fullStr | Skin Inflammation Is Not Sufficient to Break Tolerance Induced against a Novel Antigen |
| title_full_unstemmed | Skin Inflammation Is Not Sufficient to Break Tolerance Induced against a Novel Antigen |
| title_short | Skin Inflammation Is Not Sufficient to Break Tolerance Induced against a Novel Antigen |
| title_sort | skin inflammation is not sufficient to break tolerance induced against a novel antigen |
| title_unstemmed | Skin Inflammation Is Not Sufficient to Break Tolerance Induced against a Novel Antigen |
| topic | Immunology, Immunology and Allergy |
| url | http://dx.doi.org/10.4049/jimmunol.0713351 |