Costimulation of mast cells by 4-1BB, a member of the tumor necrosis factor receptor superfamily, with the high-affinity IgE receptor

被引:59
作者
Nishimoto, H
Lee, SW
Hong, H
Potter, KG
Maeda-Yamamoto, M
Kinoshita, T
Kawakami, Y
Mittler, RS
Kwon, BS
Ware, CF
Croft, M
Kawakami, T
机构
[1] La Jolla Inst Allergy & Immunol, Div Cell Biol, San Diego, CA 92121 USA
[2] La Jolla Inst Allergy & Immunol, Div Mol Immunol, San Diego, CA 92121 USA
[3] Natl Agr Res Org, Natl Inst Vegetable & Tea Sci, Shizuoka, Japan
[4] Emory Univ, Sch Med, Emory Vaccine Res Ctr, Atlanta, GA USA
[5] Univ Ulsan, Immunomodulat Res Ctr, Ulsan 680749, South Korea
关键词
D O I
10.1182/blood-2005-04-1358
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Mast cells are the major effector-cell type for immediate hypersensitivity and other forms of allergic reactions. Expression of 4-1BB, a member of the tumor necrosis factor receptor superfamily, is induced at mRNA and protein levels on stimulation through the high-affinity receptor for immunoglobulin E (IgE; Fc epsilon RI). In this study, we present evidence that agonistic anti-4-1BB antibodies can enhance Fc epsilon RI-induced cytokine production and secretion. Consistent with this, 4-1 BB-deficient mast cells exhibit reduced degranulation and cytokine production on Fc epsilon RI stimulation. Analysis of 4-1 BB ligand (4-1 BBL)deficient cells supported this notion. As a potential mechanism for these defects, we identified a defect in Ca2+ flux induced by Fc epsilon RI stimulation. The defective Ca2+ flux could be accounted for by the reduced activity of Lyn/Btk/phospholipase C-gamma 2 pathway and constitutive interactions between 4-1BB and Lyn. Therefore, Fc epsilon RI-inducible 4-1BB plays a costimulatory function together with Fc epsilon RI stimulation.
引用
收藏
页码:4241 / 4248
页数:8
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