Dascher Christopher C, Hiromatsu Kenji, Xiong Xiaowei, Morehouse Caroline, Watts Gerald, Liu Gui, McMurray David N, LeClair Kenneth P, Porcelli Steven A, Brenner Michael B
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, and Harvard Medical School, Smith 552, 1 Jimmy Fund Way, Boston, MA 02115, USA.
Int Immunol. 2003 Aug;15(8):915-25. doi: 10.1093/intimm/dxg091.
Lipids and glycolipid molecules derived from Mycobacterium tuberculosis can be presented to T cells by CD1 cell-surface molecules in humans. These lipid-specific T cells are cytolytic, secrete pro-inflammatory cytokines and have bactericidal activity. Here, we describe studies in which lipids from M. tuberculosis were incorporated into liposomes with adjuvant and tested as vaccines in a guinea pig aerosol tuberculosis challenge model. Animals vaccinated with mycobacterial lipids showed reduced bacterial burdens in the lung and spleen at 4 weeks after infection. In addition, the lungs of lipid-vaccinated animals also had significantly less pathology, with granulomatous lesions being smaller and more lymphocytic. In contrast, animals receiving only vehicle control immunizations had granulomatous lesions that were larger and often contained caseous necrotic centers. Quantification of histopathology by morphometric analysis revealed that the overall percentage of lung occupied by diseased tissue was significantly smaller in lipid-vaccinated animals as compared to vehicle control animals. In addition, the mean area of individual granulomatous lesions was found to be significantly smaller in both lipid- and bacillus Calmette-Guerin-vaccinated guinea pigs. These data support an important role for lipid antigens in the immune response to M. tuberculosis infection, potentially through the generation of CD1-restricted T cells. Immunogenic lipids thus represent a novel class of antigens that might be included to enhance the protective effects of subunit vaccine formulations.
源自结核分枝杆菌的脂质和糖脂分子可通过人类的CD1细胞表面分子呈递给T细胞。这些脂质特异性T细胞具有细胞溶解作用，能分泌促炎细胞因子并具有杀菌活性。在此，我们描述了相关研究，即将结核分枝杆菌的脂质与佐剂一起掺入脂质体中，并在豚鼠气溶胶结核攻击模型中作为疫苗进行测试。用分枝杆菌脂质接种疫苗的动物在感染后4周时，肺和脾中的细菌负荷降低。此外，接种脂质疫苗的动物肺部的病理学变化也明显较少，肉芽肿病变更小且淋巴细胞更多。相比之下，仅接受载体对照免疫的动物的肉芽肿病变更大，且常常含有干酪样坏死中心。通过形态计量分析对组织病理学进行量化显示，与载体对照动物相比，接种脂质疫苗的动物肺部患病组织所占的总体百分比明显更小。此外，在接种脂质疫苗和卡介苗的豚鼠中，单个肉芽肿病变的平均面积均明显更小。这些数据支持脂质抗原在针对结核分枝杆菌感染的免疫反应中发挥重要作用，可能是通过产生CD1限制性T细胞来实现的。因此，免疫原性脂质代表了一类新型抗原，可将其纳入以增强亚单位疫苗制剂的保护作用。
