Cunningham Adam F, Toellner Kai-Michael
University of Birmingham, Medical Research Council Centre for Immune Regulation, Birmingham B15 2TT, UK.
Clin Dev Immunol. 2003 Mar;10(1):1-6. doi: 10.1080/10446670310001598537.
The paradigm of T helper-1 (Th-1) and Th-2 cells developing from non-committed naive precursors is firmly established. Th1 cells are characterized by IFNgamma production and, in mice, the selective switching to IgG2a. Conversely IL-4 production and selective switching to IgG1 and IgE characterize Th2 cells. Analysis of Th2 induction in vitro indicates that this polarization develops gradually in T cells activated by anti-CD3 in the presence of IL-4; conversely anti-CD3 and IFNgamma induce Th1 cells. In this report, we explore evidence that indicates that the T helper cell polarization in vivo cannot solely be explained by the cytokine environment. This is provided by studying the early acquisition of Th1 and Th2 activities during responses to a mixture of Th1 and Th2-inducing antigens. It is shown that these divergent forms of T cell help can rapidly develop in cells within a single lymph node. It is argued that early polarization to show Th-1 or Th-2 behavior can be induced by signals delivered during cognate interaction between virgin T cells and dendritic cells, in the absence of type 1 or type 2 cytokines. This contrasts with the critical role of the cytokines in reinforcing the Th-phenotype and selectively expanding T helper clones.
从未分化的初始前体细胞发育而来的辅助性T细胞1（Th-1）和辅助性T细胞2（Th-2）的模式已被牢固确立。Th1细胞的特征是产生γ干扰素，在小鼠中则是选择性地转换为IgG2a。相反，Th2细胞的特征是产生白细胞介素-4以及选择性地转换为IgG1和IgE。体外Th2诱导分析表明，这种极化在存在白细胞介素-4的情况下由抗CD3激活的T细胞中逐渐发展；相反，抗CD3和γ干扰素诱导Th1细胞。在本报告中，我们探讨了表明体内辅助性T细胞极化不能仅由细胞因子环境来解释的证据。这是通过研究对Th1和Th2诱导抗原混合物的反应过程中Th1和Th2活性的早期获得情况来提供的。结果表明，这些不同形式的T细胞辅助功能可在单个淋巴结内的细胞中迅速发展。有人认为，在未成熟T细胞与树突状细胞的同源相互作用过程中传递的信号可在不存在1型或2型细胞因子的情况下诱导早期极化以表现出Th-1或Th-2行为。这与细胞因子在强化Th表型和选择性扩增辅助性T细胞克隆方面的关键作用形成对比。
