Institute of Immunology and Infection Research, University of Edinburgh, Ashworth Laboratories, Edinburgh, UK.
Trends Immunol. 2012 Apr;33(4):181-9. doi: 10.1016/j.it.2012.01.001. Epub 2012 Mar 5.
Helminth parasites survive through a combination of parasite longevity, repeated re-infection and selective immune suppression to prevent protective Th2 responses. To counteract helminth-induced immunosuppression, and to induce long-term immunological memory, understanding of the multiple regulatory pathways within the T cell compartment is needed. Extrinsic inhibition by regulatory T cells is a key element of Th2 suppression. In addition, Th2 cells in chronic regulatory environments become functionally impaired, indicating cell-intrinsic regulation, which compromises protective Th2 memory. We discuss these pathways and consider the potential for reversing unresponsiveness through stimulatory signals or replacement by new responder populations. Future vaccine or therapeutic strategies should aim to minimize extrinsic regulatory effects and simultaneously negate Th2 anergy to drive effector responses into a long-term functionally competent state.
寄生虫通过寄生虫寿命延长、反复再感染和选择性免疫抑制的组合来生存，以防止保护性 Th2 反应。为了对抗寄生虫引起的免疫抑制，并诱导长期免疫记忆，需要了解 T 细胞区室中的多种调节途径。调节性 T 细胞的外在抑制是 Th2 抑制的关键因素。此外，慢性调节环境中的 Th2 细胞功能受损，表明存在细胞内在调节，从而损害了保护性 Th2 记忆。我们讨论了这些途径，并考虑了通过刺激信号或通过新的应答细胞群替代来逆转无反应性的可能性。未来的疫苗或治疗策略应旨在最小化外在调节作用，同时消除 Th2 失能，以将效应反应驱动到长期功能健全的状态。
