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Clinical and Developmental Immunology
Volume 2012 (2012), Article ID 450738, 11 pages
http://dx.doi.org/10.1155/2012/450738
Research Article

Adaptive Immune Response to Model Antigens Is Impaired in Murine Leukocyte-Adhesion Deficiency-1 Revealing Elevated Activation Thresholds In Vivo

1Department of Dermatology and Allergic Diseases, University of Ulm, Maienweg 12, 89081 Ulm, Germany
2Department of Molecular and Cellular Sports Medicine, German Sports University, Am Sportpark Müngersdorf 6, 50933 Cologne, Germany
3Institute of Immunology, Hannover Medical School, Carl-Neuberg-Straß 1, 30625 Hannover, Germany
4Institute of Pathology, University of Leipzig, Liebigstraße, 04103 Leipzig, Germany
5Mouse Genetics and Inflammation Laboratory, Institute for Genetics, University of Cologne, Zülpicher Straß 47a, 50674 Cologne, Germany
6LIMES (Life and Medical Sciences) Institute, University of Bonn, Carl-Troll-Straß 31, 53115 Bonn, Germany
7Institute of Immunology, University of Muenster, Röntgenstraße 21, 48149 Muenster, Germany
8Department of Dermatology, University of Mainz, Langenbeckstr. 1, 55131 Mainz, Germany
9Department of Molecular Immunology, Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, 73 Tzarigradsko shose, 1113 Sofia, Bulgaria
10Department of Anatomy I, University of Cologne, Joseph-Stelzmann Straß 9, 50931 Cologne, Germany
11Faculty of Life Science, University of Manchester, Oxford Road, Manchester M13 9PT, UK

Received 15 October 2011; Accepted 6 December 2011

Academic Editor: Alexandre S. Basso

Copyright © 2012 Thorsten Peters et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.