Fitzgerald T J, Tomai M A
Department of Medical Microbiology and Immunology, School of Medicine, University of Minnesota, Duluth 55812.
Infect Immun. 1991 Nov;59(11):4180-6. doi: 10.1128/iai.59.11.4180-4186.1991.
Immune regulation during syphilitic infection is extremely complex. This paper presents findings on the early events of T-cell activation following testicular infection in rabbits. Treponema pallidum was preincubated for 24 h with nonadherent spleen cells. After being washed to remove the organisms, these spleen cells were either stimulated with concanavalin A (ConA) to induce interleukin-2 (IL-2), or added to adherent cells that were then stimulated with lipopolysaccharide to induce IL-1. Preincubation with the treponemes up-regulated nonadherent cell functions. These sensitized cells increased their IL-2 production and augmented macrophage IL-1 synthesis. In sharp contrast, if this preincubation step was omitted, down-regulation was apparent. When T. pallidum was directly incubated with nonadherent cells in the presence of ConA, reduced levels of IL-2 were detected. Nonadherent cells from infected rabbits secreted soluble suppressive factors after 48 h of in vitro incubation; these factors inhibited ConA-induced IL-2 generation as well as ConA-induced lymphocyte proliferation. At least some of this suppressive activity was attributed to transforming growth factor. In addition, when T lymphocytes were depleted, less suppression was detected. Treponemes also inhibited ConA-induced T-cell proliferation, and monophosphoryl lipid A reversed this inhibitory effect. Since monophosphoryl lipid A neutralizes T-suppressor activity, these findings further suggest a role for T-suppressor activity during syphilitic infection. Finally, T. pallidum directly stimulated IL-2 synthesis when coincubated with phorbol myristate acetate. This agent reverses the prostaglandin E2 blockage of T-helper cell protein kinase C, a necessary second messenger signal for IL-2 synthesis. In summary, T-cell functions are extremely complex and represent a composite of both stimulation and down-regulation, which occur concurrently but to different degrees.
梅毒感染期间的免疫调节极其复杂。本文介绍了兔睾丸感染后T细胞激活早期事件的研究结果。梅毒螺旋体与非黏附性脾细胞预孵育24小时。洗涤去除这些微生物后，这些脾细胞要么用刀豆球蛋白A（ConA）刺激以诱导白细胞介素-2（IL-2），要么添加到黏附细胞中，然后用脂多糖刺激以诱导IL-1。与梅毒螺旋体预孵育上调了非黏附细胞功能。这些致敏细胞增加了IL-2的产生并增强了巨噬细胞IL-1的合成。形成鲜明对比的是，如果省略这个预孵育步骤，下调是明显的。当梅毒螺旋体在ConA存在下直接与非黏附细胞孵育时，检测到IL-2水平降低。感染兔的非黏附细胞在体外孵育48小时后分泌可溶性抑制因子；这些因子抑制ConA诱导的IL-2生成以及ConA诱导的淋巴细胞增殖。这种抑制活性至少部分归因于转化生长因子。此外，当T淋巴细胞被耗尽时，检测到的抑制作用较小。梅毒螺旋体也抑制ConA诱导的T细胞增殖，单磷酰脂质A可逆转这种抑制作用。由于单磷酰脂质A中和了T抑制活性，这些发现进一步表明T抑制活性在梅毒感染中起作用。最后，当与佛波醇肉豆蔻酸酯乙酸盐共同孵育时，梅毒螺旋体直接刺激IL-2合成。该试剂逆转了前列腺素E2对T辅助细胞蛋白激酶C的阻断，蛋白激酶C是IL-2合成所需的第二信使信号。总之，T细胞功能极其复杂，代表了刺激和下调的综合作用，它们同时发生但程度不同。
