title: Adaptive immune response to model antigens is impaired in murine leukocyte-adhesion deficiency-1 revealing elevated activation thresholds in vivo.
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.
authors.affiliation: Department of Dermatology and Allergic Diseases, University of Ulm, Maienweg 12, 89081 Ulm, Germany. thorsten.peters@uni-ulm.de
authors.forename: Thorsten
authors.initials: T
authors.lastname: Peters
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.forename: Oliver
authors.initials: O
authors.lastname: Pabst
authors.forename: Claudia
authors.initials: C
authors.lastname: Wickenhauser
authors.forename: Claudia
authors.initials: C
authors.lastname: Uthoff-Hachenberg
authors.forename: Susanne V
authors.initials: SV
authors.lastname: Schmidt
authors.forename: Georg
authors.initials: G
authors.lastname: Varga
authors.forename: Stephan
authors.initials: S
authors.lastname: Grabbe
authors.forename: Daniel
authors.initials: D
authors.lastname: Kess
authors.forename: Tsvetelina
authors.initials: T
authors.lastname: Oreshkova
authors.forename: Anca
authors.initials: A
authors.lastname: Sindrilaru
authors.forename: Klaus
authors.initials: K
authors.lastname: Addicks
authors.forename: Reinhold
authors.initials: R
authors.lastname: Förster
authors.forename: Werner
authors.initials: W
authors.lastname: Müller
authors.forename: Karin
authors.initials: K
authors.lastname: Scharffetter-Kochanek
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects*; D000818:Animals; D018821:CD18 Antigens / Q000235:genetics / Q000276:immunology*; D002448:Cell Adhesion / Q000187:drug effects; D004195:Disease Models, Animal; D006241:Haptens / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology*; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D015202:Protein Engineering; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D018821:CD18 Antigens; D006241:Haptens; D007074:Immunoglobulin G; D013745:Tetanus Toxoid