4-1BB engagement costimulates NKT cell activation and exacerbates NKT cell ligand-induced airway hyperresponsiveness and inflammation
SCIE
SCOPUS
- Title
- 4-1BB engagement costimulates NKT cell activation and exacerbates NKT cell ligand-induced airway hyperresponsiveness and inflammation
- Authors
- Kim, DH; Chang, WS; Lee, YS; Lee, KA; Kim, YK; Kwon, BS; Kang, CY
- Date Issued
- 2008-02-15
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Abstract
- Multiple studies have demonstrated that 4-1BB (CD137), a member of the TNF receptor superfamily, is expressed on several immune cells including activated T cells. However, the expression and the role of 4-1BB on natural killer T (NKT) cells have not been fully characterized. In this study, it was shown that 4-1BB was not expressed on naive NKT cells but was rapidly induced on activated NKT cells by TCR engagement with alpha-galactosylceramide (alpha-GalCer). Also, 4-1BB signaling provided by 3113, an agonistic anti-4-1BB mAb, promoted NKT cell activation resulting in enhanced cytokine production of NKT cells driven by alpha-GalCer. When NKT cell-driven airway immune responses were evaluated by intranasal administration of alpha-GalCer, airway hyperresponsiveness (AHR) and lung inflammation were significantly more aggravated in mice treated with 3113 and alpha-GalCer than in mice treated with alpha-GalCer alone. These aggravations were accompanied by up-regulation of IL-4, IL-13, and IFN-gamma production. Interestingly, AHR was not developed in IL-4R alpha-deficient mice treated with alpha-GalCer with or without 3H3 but was exacerbated in WN-gamma-deficient mice. Our study suggests that 4-1BB on NKT cells functions as a costimulatory molecule and exacerbates the induction of NKT cell-mediated AHR, which is dependent on the IL-4R alpha-mediated pathway.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/29467
- DOI
- 10.4049/jimmunol.180.4.2062
- ISSN
- 0022-1767
- Article Type
- Article
- Citation
- JOURNAL OF IMMUNOLOGY, vol. 180, no. 4, page. 2062 - 2068, 2008-02-15
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