Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA.
J Immunol. 2011 Sep 1;187(5):2155-61. doi: 10.4049/jimmunol.1003235. Epub 2011 Aug 5.
Immunodeficient patients with severe burn injuries are extremely susceptible to infection with Candida albicans. In addition to Th1 cells, IL-17-producing CD4(+) T cells (Th17 cells) have recently been described as an important effector cell in host anti-Candida resistance. In this study, therefore, we tried to induce Th17 cells in cultures of severely burned patient PBMC by stimulation with the C. albicans Ag (CAg). In the results, the biomarkers for Th17 cells (IL-17 production and intracellular expression of IL-17 and retinoic acid receptor-related orphan receptor γt) were not displayed by burn patient PBMC stimulated with CAg, whereas these biomarkers of Th17 cells were detected in cultures of healthy donor PBMC stimulated with CAg. Burn patient sera were shown to be inhibitory on CAg-stimulated Th17 cell generation in healthy donor PBMC cultures; however, Th17 cells were induced by CAg in healthy donor PBMC cultures supplemented with burn patient sera that were previously treated with anti-IL-10 mAb. Also, the biomarkers of Th17 cells were not induced by CAg in healthy donor PBMC cultures supplemented with rIL-10. IL-10 was detected in serum specimens derived from severely burned patients. These results indicate that Th17 cells are not generated in burn patient PBMC cultures supplemented with CAg. IL-10, produced in response to burn injuries, is shown to be inhibitory on Th17 cell generation. The high susceptibility of severely burned patients to C. albicans infection might be influenced if burn-associated IL-10 production is intervened.
免疫缺陷的严重烧伤患者极易感染白色念珠菌。除了 Th1 细胞,新近发现的产生白介素-17 的 CD4+T 细胞(Th17 细胞)是宿主抗白色念珠菌防御的重要效应细胞。因此,在本研究中,我们试图通过用白色念珠菌抗原(CAg)刺激严重烧伤患者 PBMC 来诱导 Th17 细胞。结果显示,烧伤患者 PBMC 经 CAg 刺激后未显示 Th17 细胞的生物标志物(IL-17 产生和 IL-17 及维甲酸受体相关孤儿受体 γt 的细胞内表达),而健康供体 PBMC 经 CAg 刺激后可检测到这些 Th17 细胞的生物标志物。烧伤患者血清对健康供体 PBMC 培养物中 CAg 刺激的 Th17 细胞生成具有抑制作用;然而,在经抗白介素-10 mAb 预处理的烧伤患者血清中补充 CAg 可诱导健康供体 PBMC 中 Th17 细胞的产生。此外,在补充 rIL-10 的健康供体 PBMC 培养物中,CAg 也不能诱导 Th17 细胞的产生。IL-10 在严重烧伤患者的血清标本中被检测到。这些结果表明,在补充 CAg 的烧伤患者 PBMC 培养物中不能产生 Th17 细胞。烧伤后产生的 IL-10 被证明对 Th17 细胞的生成具有抑制作用。如果干预与烧伤相关的 IL-10 产生,严重烧伤患者对白色念珠菌感染的高度易感性可能会受到影响。