Jones D, Elloso M M, Showe L, Williams D, Trinchieri G, Scott P
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Infect Immun. 1998 Aug;66(8):3818-24. doi: 10.1128/IAI.66.8.3818-3824.1998.
Previous studies have shown the central role of interleukin 12 (IL-12) in the development of resistance to Leishmania major infection in C3H mice. We now show that during the innate immune response the lymph node cells of L. major-infected C3H mice upregulate the IL-12 receptor on CD4(+), CD8(+), and B220(+) cells. An increase in the ability of the lymph node cells to bind IL-12 correlates with 9.3- and 4.6-fold increases in the mRNA expression levels of the IL-12Rbeta1 and -beta2 subunits, respectively. In contrast, BALB/c mice, which are susceptible to L. major infection, have no increase in the ability of the lymph node cells to bind IL-12 and correspondingly smaller increases in the mRNA expression levels of the IL-12Rbeta1 and -beta2 subunits of 2- and 1.5-fold, respectively. Neutralizing IL-4 and the administration of exogenous IL-12 upregulate IL-12R expression in BALB/c mice, while the neutralization of IL-12 in C3H mice blocks increased IL-12 receptor expression. These experiments reveal an important role for the regulation of the IL-12 receptor during the innate immune response after infection of mice with a pathogen.
先前的研究表明，白细胞介素12（IL-12）在C3H小鼠对硕大利什曼原虫感染产生抗性的过程中起核心作用。我们现在发现，在天然免疫反应期间，感染硕大利什曼原虫的C3H小鼠的淋巴结细胞上调CD4(+)、CD8(+)和B220(+)细胞上的IL-12受体。淋巴结细胞结合IL-12的能力增加分别与IL-12Rβ1和-β2亚基的mRNA表达水平增加9.3倍和4.6倍相关。相比之下，易受硕大利什曼原虫感染的BALB/c小鼠的淋巴结细胞结合IL-12的能力没有增加，相应地，IL-12Rβ1和-β2亚基的mRNA表达水平分别仅增加2倍和1.5倍，增幅较小。中和IL-4并给予外源性IL-12可上调BALB/c小鼠中的IL-12R表达，而在C3H小鼠中中和IL-12则会阻断IL-12受体表达的增加。这些实验揭示了在小鼠感染病原体后的天然免疫反应期间，IL-12受体调节的重要作用。
