Human γδ T-Cell Control of Mucosal Immunity and Inflammation.
Human γδ T-Cell Control of Mucosal Immunity and Inflammation.
复制标题
DOI：
10.3389/fimmu.2018.00985
复制
发表时间：
2018
影响因子：
7.3
通讯作者：
Eberl M
中科院分区：
文献类型：
--
作者：
McCarthy NE;Eberl M
人γδ Τ细胞包括外周血中一些最常见的“抗原特异性”细胞类型，并且在微生物感染和肿瘤通常起源的粘膜屏障部位进一步富集。虽然γδ T细胞区室包括具有高度灵活的效应子功能的多个亚群，但人类粘膜组织由宿主应激响应性Vδ1+ T细胞和微生物响应性Vδ2+ T细胞主导。由于其有效的细胞毒性而被广泛认可，新出现的数据表明γδ T细胞也对下游针对病原体和肿瘤的适应性免疫产生强烈影响，特别是通过激活抗原呈递细胞和/或直接刺激其他粘膜白细胞。这些独特的功能属性和缺乏MHC限制已经引起了对γδ Τ细胞的治疗靶向的相当大的兴趣。事实上，已经在临床使用的几种药物，包括Vedolizumab、英夫利西单抗和硫唑嘌呤，可能部分归功于γδ T细胞功能的调节。最近的Vδ2+ T细胞选择性治疗的临床试验表明在人类患者中具有良好的安全性，并且随着更有效/靶向药物的继续开发，疗效将增加。关键进展将包括确定将γδ T细胞募集到特定组织的方法，以增强宿主对入侵病原体的保护，或者将这些细胞保留在循环中以限制外周炎症和/或改善对血液恶性肿瘤的反应。粘膜免疫的人γδ T细胞控制可能通过多种机制发挥作用，这些机制在其他类型的组织驻留白细胞中诱导不同的应答。了解调节这些功能的微环境信号对于开发新的基于γδ T细胞的疗法至关重要。
Human γδ T-cells include some of the most common “antigen-specific” cell types in peripheral blood and are enriched yet further at mucosal barrier sites where microbial infection and tumors often originate. While the γδ T-cell compartment includes multiple subsets with highly flexible effector functions, human mucosal tissues are dominated by host stress-responsive Vδ1+ T-cells and microbe-responsive Vδ2+ T-cells. Widely recognized for their potent cytotoxicity, emerging data suggest that γδ T-cells also exert strong influences on downstream adaptive immunity to pathogens and tumors, in particular via activation of antigen-presenting cells and/or direct stimulation of other mucosal leukocytes. These unique functional attributes and lack of MHC restriction have prompted considerable interest in therapeutic targeting of γδ T-cells. Indeed, several drugs already in clinical use, including vedolizumab, infliximab, and azathioprine, likely owe their efficacy in part to modulation of γδ T-cell function. Recent clinical trials of Vδ2+ T-cell-selective treatments indicate a good safety profile in human patients, and efficacy is set to increase as more potent/targeted drugs continue to be developed. Key advances will include identifying methods of directing γδ T-cell recruitment to specific tissues to enhance host protection against invading pathogens, or alternatively, retaining these cells in the circulation to limit peripheral inflammation and/or improve responses to blood malignancies. Human γδ T-cell control of mucosal immunity is likely exerted via multiple mechanisms that induce diverse responses in other types of tissue-resident leukocytes. Understanding the microenvironmental signals that regulate these functions will be critical to the development of new γδ T-cell-based therapies.
登录
查看更多内容
DOI：
10.1084/jem.172.1.239
发表时间：
1990-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bandeira A;Mota-Santos T;Itohara S;Degermann S;Heusser C;Tonegawa S;Coutinho A
通讯作者：
Coutinho A
DOI：
10.4049/jimmunol.1601060
发表时间：
2017-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Do JS;Kim S;Keslar K;Jang E;Huang E;Fairchild RL;Pizarro TT;Min B
通讯作者：
Min B
影响因子：
2.4
作者：
Dart RJ;Samaan MA;Powell N;Irving PM
通讯作者：
Irving PM
影响因子：
4.4
作者：
Ali, Zahida;Shao, Lingyan;Chen, Zheng W.
通讯作者：
Chen, Zheng W.
影响因子：
56.9
作者：
Bauer, S;Groh, V;Spies, T
通讯作者：
Spies, T