Interleukin-18 plays a role in both the alum-induced T helper 2 response and the T helper 1 response induced by alum-adsorbed interleukin-12
Interleukin-18 plays a role in both the alum-induced T helper 2 response and the T helper 1 response induced by alum-adsorbed interleukin-12
复制标题
DOI：
10.1046/j.1365-2567.2003.01581.x
复制
发表时间：
2003-02-01
期刊：
影响因子：
6.4
通讯作者：
Brewer, JM
中科院分区：
文献类型：
--
作者：
Pollock, KGJ;Conacher, M;Brewer, JM
先前的研究表明，由明矾佐剂诱导的抗原特异性辅助性T细胞2（Th 2）应答是不依赖于白细胞介素（IL）-4的。由于IL-18在Th 2诱导中的作用最近已被描述，除了其在增强Th 1应答中的作用之外，我们研究了在野生型和IL-18缺陷小鼠中由吸附到明矾的卵清蛋白（OVA）诱导的Th 2应答。我们的研究结果表明，虽然内源性IL-18促进明矾诱导的IL-4的生产，OVA特异性免疫球蛋白G1（IgG 1）和IgE的生产保持不受影响。此外，用明矾/IL-12吸附的OVA诱导的抗原特异性Th 1应答被证明是高度EL-18依赖性的。尽管有这些观察结果，注射BALB/c小鼠与外源性EL-18吸附到明矾/OVA没有改变IL-4或干扰素-γ的生产由T细胞和有小的影响，相对生产的IgG 1/IgG 2a抗体亚类相比，明矾/OVA接种的小鼠。然而，先前描述的IL-12和IL-18在Th 1诱导中的协同作用是明显的，因为通过IL-18的共同施用，明矾/IL-12针对吸附的OVA的Th 1促进活性大大增强。这些结果表明，虽然明矾诱导的IL-18可以促进Th 2诱导，但外源性IL-18的添加不能进一步增强明矾诱导的Th 2应答。
Previous studies have shown that the antigen-specific T helper 2 (Th2) response induced by alum adjuvants is interleukin (IL)-4 independent. As a role for IL-18 in Th2 induction has recently been described, in addition to its role in enhancing Th1 responses, we have studied the Th2 response induced by ovalbumin (OVA) adsorbed to alum in wild-type and IL-18-deficient mice. Our results indicate that while endogenous IL-18 facilitates alum-induced IL-4 production, OVA-specific immunoglobulin G1 (IgG1) and IgE production remain unaffected. Furthermore, antigen-specific Th1 responses induced with alum/IL-12-adsorbed OVA were demonstrated to be highly EL-18 dependent. Despite these observations, injection of BALB/c mice with exogenous EL-18 adsorbed to alum/OVA did not alter IL-4 or interferon-gamma production by T cells and had little effect on the relative production of IgG1/IgG2a antibody subclasses compared with alum/OVA inoculated mice. However, the previously described synergism between IL-12 and IL-18 in Th1 induction was evident as the Th1-promoting activity of alum/IL-12 against adsorbed OVA was greatly augmented by the coadministration of IL-18. These results indicate that while alum-induced IL-18 can facilitate Th2 induction, the addition of exogenous IL-18 cannot further enhance the alum-induced Th2 response.