Mainali E S, McMurray D N
Department of Medical Microbiology and Immunology, College of Medicine, Texas A&M University Health Science Center, College Station 77843-1114, USA.
Infect Immun. 1998 Mar;66(3):927-31. doi: 10.1128/IAI.66.3.927-931.1998.
Previous research has suggested that dietary protein deficiency alters resistance to experimental pulmonary tuberculosis, in part, by affecting the distribution and trafficking of antigen-reactive T cells. In this study, guinea pigs were maintained on either a protein-deficient (10% ovalbumin) or control (30% ovalbumin) diet and infected 4 to 6 weeks later with a low dose of virulent Mycobacterium tuberculosis H37Rv by the respiratory route. Monoclonal antibodies directed against the CD4 or CD8 markers on guinea pig lymphocytes were used in a flow cytofluorometric assay to determine the proportion of each subset in the peripheral circulation, spleen, and bronchotracheal lymph nodes at 4 weeks after infection. In uninfected guinea pigs, only the spleen exhibited an effect of diet on T-cell distribution, with small but consistent reductions in the proportions of both CD4 and CD8 T lymphocytes. However, following infection, protein deficiency exerted a profound effect on T-cell distribution. Malnourished, tuberculous guinea pigs harbored only 20 and 60% of the T cells (as a proportion of total lymphoid cells) found in the spleen and blood, respectively, of their well-nourished counterparts. Normal relative proportions of CD4 and CD8 cells were observed, however. In striking contrast, the bronchotracheal lymph nodes of protein-deprived guinea pigs with tuberculosis contained more than twice the numbers of T cells of control guinea pigs, and the normal CD4-to-CD8 ratio was reversed. Peripheral T-cell function, as measured by the delayed hypersensitivity skin test to tuberculin, and antigen-induced lymphoproliferation in vitro were markedly suppressed in protein-malnourished animals. Conversely, purified protein derivative-induced (but not concanavalin A-induced) proliferation was significantly enhanced in cultures of lymph node cells from protein-deprived tuberculous animals. Taken together, these results suggest that immunological abnormalities and loss of antimycobacterial resistance in the lungs of protein-deficient guinea pigs may be explained, in part, by sequestration of antigen-reactive T cells in the lymph nodes draining the site of infection.
先前的研究表明，饮食蛋白质缺乏会部分地通过影响抗原反应性T细胞的分布和运输来改变对实验性肺结核的抵抗力。在本研究中，将豚鼠分别饲养在蛋白质缺乏（10%卵清蛋白）或对照（30%卵清蛋白）饮食中，4至6周后通过呼吸道感染低剂量的强毒结核分枝杆菌H37Rv。在感染后4周，使用针对豚鼠淋巴细胞上CD4或CD8标志物的单克隆抗体进行流式细胞荧光测定，以确定外周循环、脾脏和气管支气管淋巴结中每个亚群的比例。在未感染的豚鼠中，只有脾脏显示出饮食对T细胞分布的影响，CD4和CD8 T淋巴细胞的比例均有小幅但持续的降低。然而，感染后，蛋白质缺乏对T细胞分布产生了深远影响。营养不良的结核性豚鼠脾脏和血液中的T细胞（占总淋巴细胞的比例）分别仅为营养良好的同类豚鼠的20%和60%。然而，观察到CD4和CD8细胞的相对比例正常。与之形成鲜明对比的是，患有结核病的蛋白质缺乏豚鼠的气管支气管淋巴结中的T细胞数量是对照豚鼠的两倍多，且正常的CD4与CD8比值发生了逆转。通过结核菌素迟发型超敏皮肤试验和体外抗原诱导的淋巴细胞增殖来衡量，蛋白质营养不良动物的外周T细胞功能明显受到抑制。相反，在蛋白质缺乏的结核动物的淋巴结细胞培养物中，纯化蛋白衍生物诱导的（但不是伴刀豆球蛋白A诱导的）增殖显著增强。综上所述，这些结果表明，蛋白质缺乏的豚鼠肺部的免疫异常和抗分枝杆菌抵抗力的丧失可能部分是由于抗原反应性T细胞在感染部位引流的淋巴结中滞留所致。
