T helper1/t helper2 cells and resistance/susceptibility to leishmania infection: is this paradigm still relevant?
T helper1/t helper2 cells and resistance/susceptibility to leishmania infection: is this paradigm still relevant?
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DOI：
10.3389/fimmu.2012.00080
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发表时间：
2012
影响因子：
7.3
通讯作者：
Brombacher F
中科院分区：
文献类型：
--
作者：
Alexander J;Brombacher F
20 世纪 80 年代针对大利什曼原虫的大部分工作确定了两种明显反调节的 CD4+ T 细胞群：T 辅助细胞 (h)1 和 Th2，它们分别控制对感染的抵抗力/易感性。然而，20 世纪 90 年代 IL-4−/− 小鼠的产生对这种 Th2 原型细胞因子在利什曼原虫感染的非愈合反应中的重要作用提出了质疑。 CD4+ T 细胞调节群体和进一步效应 CD4+ T 辅助群体、Th17、Th9 和 T 滤泡 (f)h 细胞的最新特征以及公认的 T 辅助细胞功能可塑性进一步增加了宿主病原体相互作用的复杂性。这些相互作用因对 CD4+ T 细胞亚群签名细胞因子作出反应的细胞的多样性以及经常受到显着不同的免疫调节控制的利什曼原虫物种的多样性而变得复杂。在本文中，我们回顾了有关 CD4+ T 细胞及其产物在利什曼原虫感染期间的作用的最新知识。特别是，我们更新了使用条件性 IL-4Rα 基因缺陷小鼠的研究，这些小鼠可以剖析细胞相互作用，从而决定感染人类的主要利什曼原虫物种的疾病结果。
Work in large part on Leishmania major in the 1980s identified two distinct apparently counter-regulatory CD4+ T cell populations, T helper (h)1 and Th2, that controlled resistance/susceptibility to infection respectively. However, the generation of IL-4−/− mice in the 1990s questioned the paramount role of this Th2 archetypal cytokine in the non-healing response to Leishmania infection. The more recent characterization of CD4+ T cell regulatory populations and further effector CD4+ T helper populations, Th17, Th9, and T follicular (f)h cells as well as the acknowledged plasticity in T helper cell function has further added to the complexity of host pathogen interactions. These interactions are complicated by the multiplicity of cells that respond to CD4+ T cell subset signatory cytokines, as well as the diversity of Leishmania species that are often subject to significantly different immune-regulatory controls. In this article we review current knowledge with regard to the role of CD4+ T cells and their products during Leishmania infection. In particular we update on our studies using conditional IL-4Rα gene-deficient mice that have allowed dissection of the cell interplay dictating the disease outcomes of the major Leishmania species infecting humans.