Adaptive Immune Response to Model Antigens Is Impaired in Murine Leukocyte-Adhesion Deficiency-1 Revealing Elevated Activation Thresholds In Vivo
Absence of β2 integrins (CD11/CD18) leads to leukocyte-adhesion deficiency-1 (LAD1), a rare primary immunodeficiency syndrome. Although extensive in vitro work has established an essential function of β2 integrins in adhesive and signaling properties for cells of the innate and adaptive immune syste...
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| Format: | Article |
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Wiley
2012-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2012/450738 |
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| author | Thorsten Peters Wilhelm Bloch Oliver Pabst Claudia Wickenhauser Claudia Uthoff-Hachenberg Susanne V. Schmidt Georg Varga Stephan Grabbe Daniel Kess Tsvetelina Oreshkova Anca Sindrilaru Klaus Addicks Reinhold Förster Werner Müller Karin Scharffetter-Kochanek |
| author_facet | Thorsten Peters Wilhelm Bloch Oliver Pabst Claudia Wickenhauser Claudia Uthoff-Hachenberg Susanne V. Schmidt Georg Varga Stephan Grabbe Daniel Kess Tsvetelina Oreshkova Anca Sindrilaru Klaus Addicks Reinhold Förster Werner Müller Karin Scharffetter-Kochanek |
| author_sort | Thorsten Peters |
| collection | DOAJ |
| description | Absence of β2 integrins (CD11/CD18) leads to leukocyte-adhesion deficiency-1 (LAD1), a rare primary immunodeficiency syndrome. Although extensive in vitro work has established an essential function of β2 integrins in adhesive and signaling properties for cells of the innate and adaptive immune system, their respective participation in an altered adaptive immunity in LAD1 patients are complex and only partly understood in vivo. Therefore, we investigated adaptive immune responses towards different T-dependent antigens in a murine LAD1 model of β2 integrin-deficiency (CD18−/−). CD18−/− mice generated only weak IgG responses after immunization with tetanus toxoid (TT). In contrast, robust hapten- and protein-specific immune responses were observed after immunization with highly haptenated antigens such as (4-hydroxy-3-nitrophenyl)21 acetyl chicken γ globulin (NP21-CG), even though regularly structured germinal centers with specificity for the defined antigens/haptens in CD18−/− mice remained absent. However, a decrease in the hapten/protein ratio lowered the efficacy of immune responses in CD18−/− mice, whereas a mere reduction of the antigen dose was less crucial. Importantly, haptenation of TT with NP (NP-TT) efficiently restored a robust IgG response also to TT. Our findings may stimulate further studies on a modification of vaccination strategies using highly haptenated antigens in individuals suffering from LAD1. |
| format | Article |
| id | doaj-art-dd47ef933310461dbbef994d266f1f9d |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Developmental Immunology |
| spelling | doaj-art-dd47ef933310461dbbef994d266f1f9d2025-02-03T01:01:33ZengWileyClinical and Developmental Immunology1740-25221740-25302012-01-01201210.1155/2012/450738450738Adaptive Immune Response to Model Antigens Is Impaired in Murine Leukocyte-Adhesion Deficiency-1 Revealing Elevated Activation Thresholds In VivoThorsten Peters0Wilhelm Bloch1Oliver Pabst2Claudia Wickenhauser3Claudia Uthoff-Hachenberg4Susanne V. Schmidt5Georg Varga6Stephan Grabbe7Daniel Kess8Tsvetelina Oreshkova9Anca Sindrilaru10Klaus Addicks11Reinhold Förster12Werner Müller13Karin Scharffetter-Kochanek14Department of Dermatology and Allergic Diseases, University of Ulm, Maienweg 12, 89081 Ulm, GermanyDepartment of Molecular and Cellular Sports Medicine, German Sports University, Am Sportpark Müngersdorf 6, 50933 Cologne, GermanyInstitute of Immunology, Hannover Medical School, Carl-Neuberg-Straß 1, 30625 Hannover, GermanyInstitute of Pathology, University of Leipzig, Liebigstraße, 04103 Leipzig, GermanyMouse Genetics and Inflammation Laboratory, Institute for Genetics, University of Cologne, Zülpicher Straß 47a, 50674 Cologne, GermanyLIMES (Life and Medical Sciences) Institute, University of Bonn, Carl-Troll-Straß 31, 53115 Bonn, GermanyInstitute of Immunology, University of Muenster, Röntgenstraße 21, 48149 Muenster, GermanyDepartment of Dermatology, University of Mainz, Langenbeckstr. 1, 55131 Mainz, GermanyDepartment of Dermatology and Allergic Diseases, University of Ulm, Maienweg 12, 89081 Ulm, GermanyDepartment of Molecular Immunology, Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, 73 Tzarigradsko shose, 1113 Sofia, BulgariaDepartment of Dermatology and Allergic Diseases, University of Ulm, Maienweg 12, 89081 Ulm, GermanyDepartment of Anatomy I, University of Cologne, Joseph-Stelzmann Straß 9, 50931 Cologne, GermanyInstitute of Immunology, Hannover Medical School, Carl-Neuberg-Straß 1, 30625 Hannover, GermanyFaculty of Life Science, University of Manchester, Oxford Road, Manchester M13 9PT, UKDepartment of Dermatology and Allergic Diseases, University of Ulm, Maienweg 12, 89081 Ulm, GermanyAbsence of β2 integrins (CD11/CD18) leads to leukocyte-adhesion deficiency-1 (LAD1), a rare primary immunodeficiency syndrome. Although extensive in vitro work has established an essential function of β2 integrins in adhesive and signaling properties for cells of the innate and adaptive immune system, their respective participation in an altered adaptive immunity in LAD1 patients are complex and only partly understood in vivo. Therefore, we investigated adaptive immune responses towards different T-dependent antigens in a murine LAD1 model of β2 integrin-deficiency (CD18−/−). CD18−/− mice generated only weak IgG responses after immunization with tetanus toxoid (TT). In contrast, robust hapten- and protein-specific immune responses were observed after immunization with highly haptenated antigens such as (4-hydroxy-3-nitrophenyl)21 acetyl chicken γ globulin (NP21-CG), even though regularly structured germinal centers with specificity for the defined antigens/haptens in CD18−/− mice remained absent. However, a decrease in the hapten/protein ratio lowered the efficacy of immune responses in CD18−/− mice, whereas a mere reduction of the antigen dose was less crucial. Importantly, haptenation of TT with NP (NP-TT) efficiently restored a robust IgG response also to TT. Our findings may stimulate further studies on a modification of vaccination strategies using highly haptenated antigens in individuals suffering from LAD1.http://dx.doi.org/10.1155/2012/450738 |
| spellingShingle | Thorsten Peters Wilhelm Bloch Oliver Pabst Claudia Wickenhauser Claudia Uthoff-Hachenberg Susanne V. Schmidt Georg Varga Stephan Grabbe Daniel Kess Tsvetelina Oreshkova Anca Sindrilaru Klaus Addicks Reinhold Förster Werner Müller Karin Scharffetter-Kochanek Adaptive Immune Response to Model Antigens Is Impaired in Murine Leukocyte-Adhesion Deficiency-1 Revealing Elevated Activation Thresholds In Vivo Clinical and Developmental Immunology |
| title | Adaptive Immune Response to Model Antigens Is Impaired in Murine Leukocyte-Adhesion Deficiency-1 Revealing Elevated Activation Thresholds In Vivo |
| title_full | Adaptive Immune Response to Model Antigens Is Impaired in Murine Leukocyte-Adhesion Deficiency-1 Revealing Elevated Activation Thresholds In Vivo |
| title_fullStr | Adaptive Immune Response to Model Antigens Is Impaired in Murine Leukocyte-Adhesion Deficiency-1 Revealing Elevated Activation Thresholds In Vivo |
| title_full_unstemmed | Adaptive Immune Response to Model Antigens Is Impaired in Murine Leukocyte-Adhesion Deficiency-1 Revealing Elevated Activation Thresholds In Vivo |
| title_short | Adaptive Immune Response to Model Antigens Is Impaired in Murine Leukocyte-Adhesion Deficiency-1 Revealing Elevated Activation Thresholds In Vivo |
| title_sort | adaptive immune response to model antigens is impaired in murine leukocyte adhesion deficiency 1 revealing elevated activation thresholds in vivo |
| url | http://dx.doi.org/10.1155/2012/450738 |
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