Lung Research, Hanson Institute, Royal Adelaide Hospital, Adelaide, SA 5006, Australia.
J Heart Lung Transplant. 2012 Aug;31(8):888-95. doi: 10.1016/j.healun.2012.04.007.
We previously showed that bronchiolitis obliterans syndrome (BOS) is associated with lack of immunosuppression of T-cell pro-inflammatory cytokines and granzyme B. We recently showed that natural killer (NK) T (NKT)-like cells are a major source of pro-inflammatory cytokines and granzymes in the blood of stable lung transplant patients. NK cells also produce these pro-inflammatory mediators, and we hypothesized that BOS may be associated with lack of immunosuppression of these pro-inflammatory mediators in NK and NKT-like cells.
Granzyme, perforin, and intracellular cytokine profiles from stable transplant recipients, patients with evidence of BOS, and healthy controls were determined using multiparameter flow cytometry.
The percentage of NK cells expressing granzymes and perforin was significantly increased in BOS patients compared with stable patients and in stable patients compared with controls (89% ± 13%, 69% ± 12%, 33% ± 14% for NK and 35% ± 19%, 12% ± 15%, and 2% ± 3% for NKT-like granzyme B producing cells for BOS, stable patients and controls, respectively). There was an increase in the percentage of NK and NKT-like cells producing interferon (IFN)-γ and tumor necrosis factor (TNF)-α in BOS compared with stable patients (36% ± 16% and 10% ± 4% for NK and 32% ± 13% and 17% ± 8% for NKT-like IFN-γ producing cells for BOS and stable patients, respectively). There was a significant correlation between increased NK IFN-γ and TNF-α and values of forced expiratory volume in 1 second.
BOS is associated with increased peripheral blood NK and NKT-like cells expressing granzymes, perforin, and Th1 pro-inflammatory cytokines. These cells may migrate to the lungs and have an impact in airway damage in BOS. Therapeutic targeting of these pro-inflammatory mediators and monitoring response longitudinally using this assay may reduce BOS.
我们之前表明，闭塞性细支气管炎综合征（BOS）与 T 细胞促炎细胞因子和颗粒酶 B 的免疫抑制缺乏有关。我们最近表明，自然杀伤（NK）T（NKT）样细胞是稳定肺移植患者血液中促炎细胞因子和颗粒酶的主要来源。NK 细胞也会产生这些促炎介质，我们假设 BOS 可能与 NK 和 NKT 样细胞中这些促炎介质的免疫抑制缺乏有关。
使用多参数流式细胞术测定稳定的移植受者、有 BOS 证据的患者和健康对照者的颗粒酶、穿孔素和细胞内细胞因子谱。
与稳定患者和与对照者相比，BOS 患者的 NK 细胞表达颗粒酶和穿孔素的比例明显增加（89%±13%、69%±12%、33%±14%用于 NK 细胞和 35%±19%、12%±15%和 2%±3%用于 NKT 样颗粒酶 B 产生细胞用于 BOS、稳定患者和对照者）。与稳定患者相比，BOS 患者 NK 和 NKT 样细胞产生干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α的比例增加（36%±16%和 10%±4%用于 NK 细胞和 32%±13%和 17%±8%用于 NKT 样 IFN-γ产生细胞用于 BOS 和稳定患者）。NK IFN-γ和 TNF-α的增加与用力呼气量第一秒的数值呈显著相关。
BOS 与表达颗粒酶、穿孔素和 Th1 促炎细胞因子的外周血 NK 和 NKT 样细胞增加有关。这些细胞可能迁移到肺部，并对 BOS 中的气道损伤产生影响。通过该检测方法对这些促炎介质进行靶向治疗并进行纵向监测，可能会减少 BOS 的发生。
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