Wierenga E A, Snoek M, Jansen H M, Bos J D, van Lier R A, Kapsenberg M L
Department of Cell Biology and Histology, University of Amsterdam, The Netherlands.
J Immunol. 1991 Nov 1;147(9):2942-9.
Eight representative T lymphocyte clones (TLC) randomly selected from previously described panels of CD4+ housedust mite Dermatophagoides pteronyssinus (Dp)-specific TLC from atopic and nonatopic donors were studied in more detail in a comparative investigation. The TLC from the atopic donors closely resembled murine type 2 Th (Th2) cells by secreting substantial IL-4, IL-5, IL-6, TNF-alpha, and granulocyte-macrophage (GM)-CSF, minimal IFN-gamma, and relatively little IL-2. In contrast, the nonatopic's TLC resembled murine type 1 Th (TH1) cells by secreting substantial IFN-gamma, IL-2, TNF-alpha, and GM-CSF, no IL-4, and little IL-5. A difference with murine Th1 cells was their additional secretion of IL-6. These cytokine profiles were consistent upon stimulation via different activation pathways including stimulation with specific Dp Ag, mitogenic lectins, and antibodies to CD2, CD3, or CD28. The observed differences in IL-2 secretion, however, were most evident upon stimulation with anti-CD28. If TLC cells were cultured with highly purified B cells and stimulated with anti-CD3 in the absence of exogenous IL-4, IgE synthesis was induced only in cultures with the atopics' Th2 clones, which could be completely abrogated by anti-IL-4. The mere presence of exogenous rIL-4, however, did not result in IgE synthesis, nor did unstimulated TLC cells alone. But if unstimulated TLC cells (that proved not to secrete detectable amounts of cytokines) were added together with rIL-4, again IgE synthesis was induced only in cultures with the atopics' Th2 clones, suggesting the involvement of an additional, as yet unidentified accessory helper function of the atopics' Th2 clones for IgE induction. Unstimulated Th2 clones showed a significantly higher expression of CD28 than the Th1 clones, but three days after stimulation, CD28 expression was elevated to comparable levels on both subsets. When added to B cells at this time point, together with rIL-4 and anti-IFN-gamma, still only the atopics' Th2 clones supported IgE synthesis, arguing against a role for CD28 in this accessory helper function. Whereas the atopics' Th2 clones were excellent helper cells for IgE induction, a unique property of the nonatopic's Th1 clones was their cytolytic activity toward autologous APC which could be induced by specific Dp Ag and by anti-CD3. The present data provide clear evidence for the existence of Th1 and Th2 cells in man.
从先前描述的来自特应性和非特应性供体的屋尘螨变应原（Dp）特异性CD4⁺T淋巴细胞克隆（TLC）库中随机选择8个代表性TLC进行更详细的比较研究。来自特应性供体的TLC通过分泌大量白细胞介素-4（IL-4）、IL-5、IL-6、肿瘤坏死因子-α（TNF-α）和粒细胞-巨噬细胞（GM）-集落刺激因子（CSF），少量干扰素-γ（IFN-γ）和相对少量的IL-2，与小鼠2型辅助性T细胞（Th2）非常相似。相比之下，非特应性供体的TLC通过分泌大量IFN-γ、IL-2、TNF-α和GM-CSF，不分泌IL-4和少量IL-5，与小鼠1型辅助性T细胞（Th1）相似。与小鼠Th1细胞的一个不同之处在于它们额外分泌IL-6。通过不同的激活途径进行刺激时，包括用特异性Dp抗原、促有丝分裂凝集素以及针对CD2、CD3或CD28的抗体进行刺激，这些细胞因子谱是一致的。然而，观察到的IL-2分泌差异在用抗CD28刺激时最为明显。如果TLC细胞与高度纯化的B细胞一起培养并用抗CD3刺激，在没有外源性IL-4的情况下，仅在含有特应性供体Th2克隆的培养物中诱导IgE合成，抗IL-4可完全消除这种合成。然而，仅仅存在外源性重组IL-4并不会导致IgE合成，单独的未刺激TLC细胞也不会。但是，如果将未刺激的TLC细胞（已证明不分泌可检测量的细胞因子）与重组IL-4一起添加，同样仅在含有特应性供体Th2克隆的培养物中诱导IgE合成，这表明特应性供体Th2克隆在IgE诱导中还存在一种额外的、尚未确定的辅助性辅助功能。未刺激的Th2克隆显示出比Th1克隆显著更高的CD28表达，但在刺激三天后，两个亚群的CD28表达都升高到了相当的水平。在这个时间点将其添加到B细胞中，同时加入重组IL-4和抗IFN-γ，仍然只有特应性供体的Th2克隆支持IgE合成，这表明CD28在这种辅助性辅助功能中不起作用。虽然特应性供体的Th2克隆是IgE诱导的优秀辅助细胞，但非特应性供体Th1克隆的一个独特特性是它们对自体抗原呈递细胞（APC）的细胞溶解活性，这可由特异性Dp抗原和抗CD3诱导。目前的数据为人体中存在Th1和Th2细胞提供了明确的证据。
