Adams L B, Gillis T P, Hwang D H, Krahenbuhl J L
Gillis W. Long Hansen's Disease Center Laboratory Research Branch at Louisiana State University, Baton Rouge 70894, USA.
Infect Immun. 1997 Apr;65(4):1152-7. doi: 10.1128/iai.65.4.1152-1157.1997.
Results from animal and in vitro studies suggest that essential fatty acid (EFA) deficiency enhances cell-mediated immunity by reducing production of prostaglandins with immunosuppressive actions. However, direct experimental evidence that EFA deficiency enhances T-lymphocyte function in vivo has not been obtained. In this study, athymic (nu/nu) mice were infected in the footpads with Mycobacterium leprae and fed a linoleic acid-free diet. These mice, and infected nu/nu mice on control diets, were given an adoptive transfer of M. leprae-primed, T-cell-enriched lymphocytes. After 2 weeks, M. leprae bacilli were harvested from the recipient mice and bacterial viability was determined by the BACTEC system. M. leprae recovered from recipient mice fed control diets displayed little reduction in metabolic activity. In contrast, M. leprae from recipient mice fed the EFA-deficient (EFAD) diet exhibited markedly reduced viability. In vitro, donor cells from M. leprae-primed mice secreted elevated levels of gamma interferon upon exposure to the bacilli. These cells also exhibited an enhanced proliferative response, which was reduced by exogenous prostaglandin E2 (PGE2). In addition, M. leprae-infected granuloma macrophages (Mphi) from EFAD recipient nu/nu mice secreted significantly less PGE2 than granuloma Mphi from mice on control diets. These data suggest that enhanced levels of Mphi-generated PGE2, induced by M. leprae or its constituents, could act as an endogenous negative modulator of the immune response occurring in the microenvironment of the lepromatous granuloma.
动物和体外研究结果表明，必需脂肪酸（EFA）缺乏通过减少具有免疫抑制作用的前列腺素生成来增强细胞介导的免疫。然而，尚未获得EFA缺乏在体内增强T淋巴细胞功能的直接实验证据。在本研究中，无胸腺（nu/nu）小鼠足垫接种麻风分枝杆菌，并给予无亚油酸饮食。这些小鼠以及感染后食用对照饮食的nu/nu小鼠接受了经麻风分枝杆菌致敏、富含T细胞的淋巴细胞的过继转移。2周后，从受体小鼠中收获麻风分枝杆菌，并通过BACTEC系统测定细菌活力。从食用对照饮食的受体小鼠中回收的麻风分枝杆菌代谢活性几乎没有降低。相比之下，从食用EFA缺乏（EFAD）饮食的受体小鼠中分离出的麻风分枝杆菌活力明显降低。在体外，来自经麻风分枝杆菌致敏小鼠的供体细胞在接触杆菌后分泌升高水平的γ干扰素。这些细胞还表现出增强的增殖反应，外源性前列腺素E2（PGE2）可使其降低。此外，来自EFAD受体nu/nu小鼠的麻风分枝杆菌感染的肉芽肿巨噬细胞（Mphi）分泌的PGE2明显少于食用对照饮食小鼠的肉芽肿Mphi。这些数据表明，由麻风分枝杆菌或其成分诱导的Mphi产生的PGE2水平升高可能作为瘤型肉芽肿微环境中发生的免疫反应的内源性负调节剂。
