Anti-CD23 monoclonal antibody, lumiliximab, inhibited allergen-induced responses in antigen-presenting cells and T cells from atopic subjects

Jill A Poole, Jianfeng Meng, Mitchell Reff, Mary C. Spellman, Lanny J. Rosenwasser

Research output: Contribution to journalArticle

71 Citations (Scopus)

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-1β, TNF-α, 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-1β (P < .003) and TNF-α (P = .05) and the TH2 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). Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)780-788
Number of pages9
JournalJournal of Allergy and Clinical Immunology
Volume116
Issue number4
DOIs
StatePublished - Oct 1 2005

Fingerprint

Antigen-Presenting Cells
Allergens
T-Lymphocytes
Cytokines
U937 Cells
Interleukin-5
HLA-DR Antigens
Interleukin-1
Antibodies
lumiliximab
Cell Line
Blocking Antibodies
Immunoglobulin E
Flow Cytometry
Hypersensitivity
Cell Proliferation
Lymphocytes

Keywords

  • Antigen-presenting cell
  • CD23
  • Costimulatory molecule
  • Lumiliximab
  • T-cell response

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Anti-CD23 monoclonal antibody, lumiliximab, inhibited allergen-induced responses in antigen-presenting cells and T cells from atopic subjects. / Poole, Jill A; Meng, Jianfeng; Reff, Mitchell; Spellman, Mary C.; Rosenwasser, Lanny J.

In: Journal of Allergy and Clinical Immunology, Vol. 116, No. 4, 01.10.2005, p. 780-788.

Research output: Contribution to journalArticle

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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-1β, TNF-α, 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-1β (P < .003) and TNF-α (P = .05) and the TH2 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). Conclusion: 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.",
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AU - Meng, Jianfeng

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AU - Spellman, Mary C.

AU - Rosenwasser, Lanny J.

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