title: Anti-CD23 monoclonal antibody, lumiliximab, inhibited allergen-induced responses in antigen-presenting cells and T cells from atopic subjects.
abstract: BACKGROUND
  CD23 plays a role in the regulation of IgE production and allergy-induced immune and inflammatory responses. A novel anti-CD23 monoclonal antibody, lumiliximab, is a potential therapeutic antibody recently demonstrated to be safe in human beings.
  
  
  OBJECTIVE
  This study investigated the effects of lumiliximab on allergen-induced immune responses from atopic subjects compared with blocking HLA-DR and costimulatory molecules, CD80 and CD86.
  
  
  METHODS
  Allergen-stimulated PBMCs from atopic subjects were pretreated with lumiliximab or antibodies to CD80, CD86, and HLA-DR. Cultures were analyzed for cell proliferation and IL-1beta, TNF-alpha, and IL-5 cytokine secretion. An allergen-specific T-cell line was developed and analyzed for lymphocyte proliferation in response to allergen with or without lumiliximab. Lumiliximab's effect on CD86 expression was evaluated by flow cytometry in the U937 monocytic cell line.
  
  
  RESULTS
  Lumiliximab reduced allergen-induced PBMC proliferation by 50% (n = 6; P = .006). In addition, cultures pretreated with lumiliximab had a reduction in the proinflammatory cytokines IL-1beta (P < .003) and TNF-alpha (P = .05) and the T(H)2 cytokine IL-5 (P = .002). Blocking CD86 resulted in greater reduction in proliferation than lumiliximab (P = .003) but similar effects in cytokine secretion. The anti-CD80 blocking antibody had no effect on cytokine production but did reduce proliferation. Furthermore, the addition of lumiliximab to cytokine stimulated U937 cells reduced surface expression of CD86 (P = .012).
  
  
  CONCLUSIONS
  These results indicate that the anti-CD23 mAb, lumiliximab, may be involved in modulating antigen presenting cells and reducing TH2-type immune responses. The use of this antibody may provide clinical benefit for treating allergic diseases.
authors.affiliation: National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Division of Allergy and Clinical Immunology, Department of Medicine, Denver, USA. japoole@unmc.edu
authors.forename: Jill A
authors.initials: JA
authors.lastname: Poole
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Meng
authors.forename: Mitchell
authors.initials: M
authors.lastname: Reff
authors.forename: Mary C
authors.initials: MC
authors.lastname: Spellman
authors.forename: Lanny J
authors.initials: LJ
authors.lastname: Rosenwasser
mesh_terms: D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000628:therapy*; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D017455:Receptors, IgE / Q000037:antagonists & inhibitors* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D020298:U937 Cells
chemical_list: D000485:Allergens; D000911:Antibodies, Monoclonal; D016207:Cytokines; D018836:Inflammation Mediators; D017455:Receptors, IgE; C509683:lumiliximab