Wahl Sharon M, Wen Jie, Moutsopoulos Niki
Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4352, USA.
Immunol Rev. 2006 Oct;213:213-27. doi: 10.1111/j.1600-065X.2006.00437.x.
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.
功能上受到阻碍的免疫反应或免疫赦免部位不再被认为依赖于特定的解剖学因素，相反，它们可以在免疫调节细胞聚集并表达或释放能够改变宿主对外来抗原反应的产物的任何位置形成。在协调这些异位免疫抑制部位中起关键作用的分子包括转化生长因子-β（TGF-β），它是一种分泌型和细胞相关的多肽，在固有免疫和适应性免疫中具有多种作用。虽然TGF-β介导的免疫抑制途径在启动和控制免疫反应以及维持免疫稳态方面有益，但它可能会掩盖免疫监视机制，导致无法识别或充分应对自身、外来或肿瘤相关抗原。CD4+CD25+Foxp3+调节性T细胞是TGF-β介导的抑制作用的主要传递者，在浸润性肿瘤和其他免疫赦免部位中存在，它们在这些部位影响CD8+T细胞、CD4+辅助性（Th）1、Th2和Th17细胞、自然杀伤细胞以及髓系细胞，以编排和/或破坏宿主防御。确定区分局部免疫赦免动态建立的细胞来源、作用机制和网络，对于开发战略方法以减少或增强这些致耐受性事件以获得治疗益处至关重要。
