TGF-beta: a mobile purveyor of immune privilege.
TGF-beta: a mobile purveyor of immune privilege.
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DOI：
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发表时间：
2006
影响因子：
8.7
通讯作者：
S. Wahl;J. Wen;N. Moutsopoulos
中科院分区：
文献类型：
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作者：
S. Wahl;J. Wen;N. Moutsopoulos
功能性屏障免疫反应或免疫特权位点不再被认为依赖于特定的解剖学考虑，而是它们可以在免疫调节细胞聚集并表达或释放能够偏离宿主对外来抗原反应的产物的任何位置中发展。转化生长因子-β (TGF-β) 是参与协调这些异位免疫抑制位点的关键分子之一，它是一种分泌性细胞相关多肽，在先天性和适应性免疫中具有多种作用。虽然有利于启动和控制免疫反应以及维持免疫稳态，但 TGF-β 介导的免疫抑制途径可能会掩盖免疫监视机制，导致无法识别或充分响应自身、外来或肿瘤相关抗原。 CD4+CD25+Foxp3+调节性T细胞是TGF-β介导的抑制的主要提供者，存在于浸润性肿瘤和其他免疫特权位点，在那里它们影响CD8+T细胞； CD4+ T 辅助细胞 (Th)1、Th2 和 Th17 细胞；自然杀伤细胞；以及骨髓谱系细胞来编排和/或破坏宿主防御。定义区分局部免疫特权动态建立的细胞来源、作用机制和网络对于开发减少或修饰这些耐受事件以获得治疗益处的战略方法至关重要。
Functionally barricaded immune responses or sites of immune privilege are no longer considered dependent on specific anatomical considerations, but rather, they can develop in any location where immunoregulatory cells congregate and express or release products capable of deviating the host response to foreign antigens. Among the pivotal molecules involved in orchestrating these ectopic sites of immune suppression is transforming growth factor-beta (TGF-beta), a secreted and cell-associated polypeptide with a multiplicity of actions in innate and adaptive immunity. While beneficial in initiating and controlling immune responses and maintaining immune homeostasis, immunosuppressive pathways mediated by TGF-beta may obscure immune surveillance mechanisms, resulting in failure to recognize or respond adequately to self, foreign, or tumor-associated antigens. CD4+CD25+Foxp3+ regulatory T cells represent a dominant purveyor of TGF-beta-mediated suppression and are found in infiltrating tumors and other sites of immune privilege, where they influence CD8+ T cells; CD4+ T-helper (Th)1, Th2, and Th17 cells; natural killer cells; and cells of myeloid lineage to choreograph and/or muck up host defense. Defining the cellular sources, mechanisms of action, and networking that distinguish the dynamic establishment of localized immune privilege is vital for developing strategic approaches to diminish or to embellish these tolerogenic events for therapeutic benefit.