Impaired dendritic cell function resulting from chronic undernutrition disrupts the antigen-specific immune response in mice
Impaired dendritic cell function resulting from chronic undernutrition disrupts the antigen-specific immune response in mice
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DOI：
10.1093/jn/137.3.671
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发表时间：
2007-03-01
影响因子：
4.2
通讯作者：
Onji, Morikazu
中科院分区：
文献类型：
--
作者：
Niiya, Tetsuji;Akbar, Sk. Md. Fazle;Onji, Morikazu
我们检测了蛋白质能量营养不良小鼠(PEM小鼠)与营养不良(对照)小鼠相比，抗原特异性免疫反应是否较低。通过分析抗原提呈树突状细胞(DC)的功能，探讨PEM小鼠抗原特异性免疫反应降低的机制。雄性C57BL/6小鼠每日进食量相当于随意进食对照组小鼠平均摄食量的70%，持续52wk，从而产生PEM小鼠。用含乙肝表面抗原(HBs)的乙肝疫苗免疫PEM小鼠和对照组小鼠，免疫后52wk和58wk分别检测其体液和细胞免疫应答。采用淋巴细胞增殖试验检测淋巴细胞和DC的功能。在52wk的食物限制后，PEM小鼠的体重比对照组减轻了49%，几乎没有皮下脂肪，严重的肌肉萎缩和脾萎缩。作为乙肝疫苗免疫的结果，所有对照小鼠都在血清中产生了抗HBs的抗体，并在脾中产生了HBs抗原特异的淋巴细胞。然而，PEM小鼠对乙肝疫苗免疫几乎没有反应。PEM组小鼠脾树突状细胞数量、T淋巴细胞刺激活性及产生IL-12p70和干扰素-γ的能力均低于对照组(P<0.05)。我们认为，慢性营养不良扰乱了抗原特异性免疫反应，这种破坏至少可以部分归因于DC频率降低和功能受损。
We examined whether antigen-specific immune responses are lower in mice with protein energy malnutrition (PEM mice) compared with nourished (control) mice. The mechanisms underlying reduced antigen-specific immune responses of PEM mice were evaluated through analysis of the functional capacities of antigen-presenting dendritic cells (DC). PEM mice were produced by subjecting male C57BL/6 mice for 52 wk to a daily food intake equivalent to 70% of the mean amount consumed by the control mice that consumed food ad libitum. PEM mice and control mice were immunized with hepatitis B vaccine containing hepatitis B surface antigen (HBsAg) at 52 wk and humoral and cellular immune responses to HBsAg were evaluated at 58wk. Lymphoproliferative assays were performed to assess the functional capacities of lymphocytes and DC. After 52 wk of food restriction, PEM mice had a 49% lower body weight than controls, almost no subcutaneous fat, severe muscle wasting, and atrophied spleen. All control mice developed antibodies to HBsAg (anti-HBs) in the sera and HBsAg-specific lymphocytes in the spleen as a result of immunization with the hepatitis B vaccine. PEM mice, however, were almost unresponsive to immunization with the hepatitis B vaccine. In PEM mice, the numbers of spleen DC, the T lymphocyte stimulatory capacities of DC, and their production of IL-12p70 and IFN-gamma was less than those of control mice (P < 0.05). We suggest that chronic undernutrition disrupts antigen-specific immune responses and that this disruption can be attributed at least in part to reduced frequencies and impaired functions of DC.