O'Quinn Darrell B, Palmer Matthew T, Lee Yun Kyung, Weaver Casey T
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Adv Immunol. 2008;99:115-63. doi: 10.1016/S0065-2776(08)00605-6.
Recently, a paradigm shift has emerged in T-cell-mediated adaptive immunity. On the heels of the discovery of T cells with immunosuppressive function, so-called regulatory T cells (Tregs), the diversity of effector cells has expanded to include a third helper T cell, termed Th17. The appreciation that Th17 cells are products of a distinct effector pathway depended critically on observations made during investigations of mouse models of autoimmunity, advanced by discovery of the cytokines IL-17 and IL-23. These studies understandably led investigators to highlight the role played by Th17 cells in autoimmunity. Yet while the dysfunctional behavior of this phenotype as a contributor to inflammatory disease remains a central issue, this pathway evolved to meet a need for host protection against potential pathogens. It has become apparent that the Th17 pathway promotes host defense against certain extracellular bacteria and fungi, but more recent studies also implicate a role in protection against some protozoa and viruses. Here we review the experimental history that ultimately uncovered the existence and nature of Th17 cells, and then turn the reader's attention to what is currently known about Th17 cells as a bulwark against pathogens.
最近,T细胞介导的适应性免疫出现了范式转变。在发现具有免疫抑制功能的T细胞(即所谓的调节性T细胞,Tregs)之后,效应细胞的多样性得到了扩展,包括第三种辅助性T细胞,即Th17细胞。认识到Th17细胞是一条独特效应途径的产物,这在很大程度上依赖于在自身免疫小鼠模型研究过程中所做的观察,而这一研究因细胞因子IL-17和IL-23的发现而取得进展。可以理解,这些研究促使研究人员强调Th17细胞在自身免疫中的作用。然而,尽管这种表型作为炎症性疾病的一个促成因素的功能失调行为仍然是一个核心问题,但这条途径的进化是为了满足宿主抵御潜在病原体的需要。显而易见,Th17途径促进宿主抵御某些细胞外细菌和真菌,但最近的研究也表明它在抵御一些原生动物和病毒方面也发挥作用。在这里,我们回顾了最终揭示Th17细胞存在及其性质的实验历程,然后将读者的注意力转向目前已知的Th17细胞作为抵御病原体的堡垒的相关情况。