白细胞介素-16和CD28/B7共刺激在轻度和中度哮喘患者支气管黏膜中T淋巴细胞趋化活性产生中的不同作用。

Differential roles of IL-16 and CD28/B7 costimulation in the generation of T-lymphocyte chemotactic activity in the bronchial mucosa of mild and moderate asthmatic individuals.

作者信息

Dent Gordon, Hosking Lisa A, Lordan James L, Steel Mark D, Cruikshank William W, Center David M, Ellis Jonathan H, Holgate Stephen T, Davies Donna E, Djukanović Ratko

机构信息

Respiratory Cell & Molecular Biology Section, Division of Infection Inflammation & Repair, University of Southampton School of Medicine, United Kingdom.

出版信息

J Allergy Clin Immunol. 2002 Dec;110(6):906-14. doi: 10.1067/mai.2002.130049.

DOI:10.1067/mai.2002.130049

PMID:12464958

Abstract

BACKGROUND

IL-16 is an important T-cell chemotactic cytokine in asthmatic airways; its release from allergen-stimulated bronchial mucosa in mild asthma has been shown to be dependent on CD28/B7 costimulation.

OBJECTIVE

We have extended our previous studies to investigate the role of IL-16 and CD28/B7 costimulation in T-lymphocyte chemotactic activity (TLCA) released from the bronchial mucosa in more severe asthma.

METHODS

TLCA was determined in the supernatants of induced sputum and allergen-stimulated bronchial mucosal explants from healthy volunteers and volunteers with mild and moderately severe asthma by means of a Boyden chamber technique. The contribution of IL-16 to the activity was evaluated through use of a neutralizing monoclonal antibody; the contribution of CD28/B7 costimulation to allergen-induced release of TLCA was determined through use of CTLA4-Ig fusion protein and neutralizing monoclonal antibodies to CD80 (B7.1) and CD86 (B7.2).

RESULTS

Induced sputum and unstimulated explants from asthmatic subjects generated significant spontaneous TLCA (P <.05). Both mild and moderate asthmatic explants showed significantly elevated Dermatophagoides pteronyssinus -induced release of TLCA, but only in mild asthma could sputum and allergen-stimulated explant TLCA be inhibited by anti-IL-16 (median inhibition, 39% and 59%; P <.05). In addition, allergen released significant quantities of IL-16 from mild asthmatic explants (P <.05) but not from moderate asthmatic explants. Antibodies to the CD28 counter-ligands CD80 and CD86 inhibited allergen-induced release of TLCA in mild asthmatic explants by 94% (P <.05) and 62%, but TLCA release from moderate asthmatic explants was unaffected by CTLA4-Ig.

CONCLUSION

These results show that TLCA release in moderate asthmatic airways, in contrast to mild asthmatic airways, is not dependent on CD28/B7 costimulation and does not involve IL-16.

摘要

背景

白细胞介素-16（IL-16）是哮喘气道中一种重要的T细胞趋化细胞因子；在轻度哮喘中，其从变应原刺激的支气管黏膜释放已被证明依赖于CD28/B7共刺激。

目的

我们扩展了之前的研究，以调查IL-16和CD28/B7共刺激在更严重哮喘中支气管黏膜释放的T淋巴细胞趋化活性（TLCA）中的作用。

方法

通过Boyden小室技术，在健康志愿者以及轻度和中度严重哮喘志愿者的诱导痰上清液和变应原刺激的支气管黏膜外植体中测定TLCA。通过使用中和单克隆抗体评估IL-16对活性的贡献；通过使用CTLA4-Ig融合蛋白以及针对CD80（B7.1）和CD86（B7.2）的中和单克隆抗体，确定CD28/B7共刺激对变应原诱导的TLCA释放的贡献。

结果

哮喘受试者的诱导痰和未刺激的外植体产生显著的自发TLCA（P<.05）。轻度和中度哮喘外植体均显示，粉尘螨诱导的TLCA释放显著升高，但仅在轻度哮喘中，痰和变应原刺激的外植体TLCA可被抗IL-16抑制（中位抑制率分别为39%和59%；P<.05）。此外，变应原从轻度哮喘外植体中释放出大量IL-16（P<.05），但从中度哮喘外植体中未释放。针对CD28配体CD80和CD86的抗体在轻度哮喘外植体中抑制变应原诱导的TLCA释放达94%（P<.05）和62%，但CTLA4-Ig对中度哮喘外植体的TLCA释放无影响。