Smith Karen M, Brewer James M, Rush Catherine M, Riley Jillian, Garside Paul
Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, Glasgow, Scotland, United Kingdom.
J Immunol. 2004 Aug 1;173(3):1640-6. doi: 10.4049/jimmunol.173.3.1640.
The description of Th1 and Th2 T cell subsets rationalized the inverse correlation between humoral and cell-mediated immunity. Although Th1 cells were described to support cell-mediated immune responses, their role in supporting certain B cell responses was firmly established. However, there is now a prevailing preconception that provision of B cell help is entirely the domain of Th2 cells and that Th1 cells lack this capacity. Previous studies demonstrated that immunization using aluminum hydroxide adjuvants induces Ag-specific Th2 responses, whereas incorporation of IL-12 with aluminum hydroxide produces a Th1 inducing adjuvant. By immunizing TCR transgenic recipient mice in this fashion, we have generated Ag-specific, traceable Th1 and Th2 cells in vivo and assessed their follicular migration and ability to support B cell responses. In this study we have shown that in vivo polarized Th1 and Th2 cells clonally expand to similar levels and migrate into B cell follicles in which they support B cell responses to a similar degree. Critically, we present direct evidence that in vivo polarized, IFN-gamma secreting Th1 cells migrate into B cell follicles where they can interact with Ag-specific B cells.
Th1和Th2 T细胞亚群的描述解释了体液免疫和细胞介导免疫之间的负相关关系。虽然Th1细胞被认为可支持细胞介导的免疫反应,但其在支持某些B细胞反应中的作用也已得到明确证实。然而,目前普遍存在一种先入之见,即提供B细胞辅助完全是Th2细胞的领域,而Th1细胞缺乏这种能力。先前的研究表明,使用氢氧化铝佐剂进行免疫可诱导抗原特异性Th2反应,而将白细胞介素-12与氢氧化铝混合则可产生诱导Th1的佐剂。通过以这种方式免疫TCR转基因受体小鼠,我们在体内产生了抗原特异性、可追踪的Th1和Th2细胞,并评估了它们向滤泡的迁移情况以及支持B细胞反应的能力。在本研究中,我们表明,体内极化的Th1和Th2细胞克隆扩增至相似水平,并迁移至B细胞滤泡,在其中它们支持B细胞反应的程度相似。至关重要的是,我们提供了直接证据,证明体内极化的、分泌干扰素-γ的Th1细胞迁移至B细胞滤泡,在那里它们可以与抗原特异性B细胞相互作用。