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来自囊性纤维化患者和健康供体的γδ T淋巴细胞在对铜绿假单胞菌的反应中是肿瘤坏死因子-α和干扰素-γ的高产细胞。

Gammadelta T lymphocytes from cystic fibrosis patients and healthy donors are high TNF-alpha and IFN-gamma-producers in response to Pseudomonas aeruginosa.

作者信息

Raga Salvador, Julià M Rosa, Crespí Catalina, Figuerola Joan, Martínez Natalia, Milà Joan, Matamoros Núria

机构信息

Immunology Service, Son Dureta Hospital, Palma de Mallorca, Balearic Islands, Spain.

出版信息

Respir Res. 2003;4(1):9. doi: 10.1186/1465-9921-4-9. Epub 2003 Sep 8.

Abstract

BACKGROUND

Gammadelta T cells have an important immunoregulatory and effector function through cytokine release. They are involved in the responses to Gram-negative bacterium and in protection of lung epithelium integrity. On the other hand, they have been implicated in airway inflammation.

METHODS

The aim of the present work was to study intracytoplasmic IL-2, IL-4, IFN-gamma and TNF-alpha production by gammadelta and alphabeta T lymphocytes from cystic fibrosis patients and healthy donors in response to Pseudomonas aeruginosa (PA). Flow cytometric detection was performed after peripheral blood mononuclear cells (PBMC) culture with a cytosolic extract from PA and restimulation with phorbol ester plus ionomycine. Proliferative responses, activation markers and receptor usage of gammadelta T cells were also evaluated.

RESULTS

The highest production of cytokine was of TNF-alpha and IFN-gamma, gammadelta being better producers than alphabeta. No differences were found between patients and controls. The Vgamma9delta2 subset of gammadelta T cells was preferentially expanded. CD25 and CD45RO expression by the alphabeta T subset and PBMC proliferative response to PA were defective in cystic fibrosis lymphocytes.

CONCLUSION

Our results support the hypothesis that gammadelta T lymphocytes play an important role in the immune response to PA and in the chronic inflammatory lung reaction in cystic fibrosis patients. They do not confirm the involvement of a supressed Th1 cytokine response in the pathogenesis of this disease.

摘要

背景

γδ T细胞通过释放细胞因子发挥重要的免疫调节和效应功能。它们参与对革兰氏阴性菌的反应以及保护肺上皮完整性。另一方面,它们与气道炎症有关。

方法

本研究的目的是研究囊性纤维化患者和健康供体的γδ和αβ T淋巴细胞在响应铜绿假单胞菌(PA)时胞内白细胞介素-2、白细胞介素-4、干扰素-γ和肿瘤坏死因子-α的产生情况。在用PA的胞质提取物培养外周血单核细胞(PBMC)并使用佛波酯加离子霉素进行再刺激后,进行流式细胞术检测。还评估了γδ T细胞的增殖反应、激活标志物和受体使用情况。

结果

细胞因子产生最多的是肿瘤坏死因子-α和干扰素-γ,γδ T细胞比αβ T细胞产生得更多。患者和对照组之间未发现差异。γδ T细胞的Vγ9δ2亚群优先扩增。在囊性纤维化淋巴细胞中,αβ T亚群的CD25和CD45RO表达以及PBMC对PA的增殖反应存在缺陷。

结论

我们的结果支持以下假设,即γδ T淋巴细胞在对PA的免疫反应以及囊性纤维化患者的慢性炎症性肺反应中起重要作用。它们并未证实Th1细胞因子反应受抑制参与了该疾病的发病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9222/203157/a6463ae51e41/1465-9921-4-9-1.jpg

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