Chakkalath H R, Titus R G
Department of Tropical Public Health, Harvard School of Public Health, Boston, MA 02115.
J Immunol. 1994 Nov 15;153(10):4378-87.
We studied the ability of resident peritoneal M phi, parasitized in vitro with Leishmania major, to present Ag to three Th2-type T cell clones that are specific for non-leishmanial Ags. Results indicated that L. major-infected M phi enhanced the proliferation and IL-4 secretion of Th2 T cells in response to stimulation with their cognate Ag. Augmentation of Th2 T cell proliferation was seen in Ag-driven responses but not in mitogenic Con A stimulation. Furthermore, live L. major promastigotes and amastigotes, but not killed parasites, augmented the Th2 T cell response. To delineate the augmentative effect of L. major-infected M phi for Th2 T cell activation, we analyzed the cytokines produced by infected M phi in the presence or absence of Th2 T cell clones. The supernatants contained IL-1 but not IL-6 or IL-10. Interestingly, addition of a neutralizing anti-IL-1 alpha mAb to the cultures reduced the augmentative effect for Th2 proliferation. Moreover, additional experiments showed that IL-1 alpha could substitute for L. major and enhance T cell activation in cultures consisting of Th2 cells, normal M phi, and Ag. Thus, our study shows that L. major-infected M phi present Ags in a manner that augments Th2 T cell proliferation and IL-4 synthesis, and that the phenomenon is at least in part mediated by IL-1 secreted by the infected M phi. For purposes of comparison, two non-leishmanial Ag specific Th1-type T cell clones were stimulated with L. major-infected M phi. Our data, as already reported by others, showed that infected M phi inhibited the response of Th1 T cells to their cognate Ag. Taken together, this report shows that leishmanial-infected M phi favor the activation of Th2 T cells over Th1 cells and that Th1 and Th2 cells require distinct activation signals from M phi.
我们研究了体外被硕大利什曼原虫寄生的腹腔巨噬细胞向三种对非利什曼原虫抗原特异的Th2型T细胞克隆呈递抗原的能力。结果表明，被硕大利什曼原虫感染的巨噬细胞在其同源抗原刺激下增强了Th2 T细胞的增殖和IL-4分泌。在抗原驱动的反应中可见Th2 T细胞增殖增强，但在促有丝分裂的刀豆蛋白A刺激中未见增强。此外，活的硕大利什曼原虫前鞭毛体和无鞭毛体可增强Th2 T细胞反应，但死的寄生虫则不能。为了阐明被硕大利什曼原虫感染的巨噬细胞对Th2 T细胞激活的增强作用，我们分析了在有或无Th2 T细胞克隆存在的情况下被感染巨噬细胞产生的细胞因子。上清液中含有IL-1，但不含IL-6或IL-10。有趣的是，向培养物中加入中和性抗IL-1α单克隆抗体可降低对Th2增殖的增强作用。此外，进一步的实验表明，IL-1α可替代硕大利什曼原虫并增强由Th2细胞、正常巨噬细胞和抗原组成的培养物中的T细胞激活。因此，我们的研究表明，被硕大利什曼原虫感染的巨噬细胞以增强Th2 T细胞增殖和IL-4合成的方式呈递抗原，并且该现象至少部分由被感染巨噬细胞分泌的IL-1介导。为作比较，用被硕大利什曼原虫感染的巨噬细胞刺激两种非利什曼原虫抗原特异的Th1型T细胞克隆。我们的数据，正如其他人已报道的，表明被感染的巨噬细胞抑制Th1 T细胞对其同源抗原的反应。综上所述，本报告表明，利什曼原虫感染的巨噬细胞更有利于Th2 T细胞而非Th1细胞的激活，并且Th1和Th2细胞需要来自巨噬细胞的不同激活信号。
