Jiang Yi, Jolly Pauline E, Ellis William O, Wang Jia-Sheng, Phillips Timothy D, Williams Jonathan H
Department of Epidemiology and International Health, School of Public Health, University of Alabama, Birmingham, AL 35294, USA.
Int Immunol. 2005 Jun;17(6):807-14. doi: 10.1093/intimm/dxh262. Epub 2005 Jun 8.
Although aflatoxins (AFs) have been shown to be immune-suppressive agents in animals, the potential role of AFs in modifying the distribution and function of leukocyte subsets in humans has never been assessed. We examined the cellular immune status of 64 Ghanaians in relation to levels of aflatoxin B1 (AFB1)-albumin adducts in plasma. The percentages of leukocyte immunophenotypes in peripheral blood, CD4+ T cell proliferative response, CD4+ T(h) and CD8+ T cell cytokine profiles and monocyte phagocytic activity were measured using flow cytometry. NK cell cytotoxic function was determined by perforin and tumor necrosis factor-alpha expression in CD3-CD56+ NK cells. AFB1-albumin adducts levels ranged from 0.3325 to 2.2703 (mean = 0.9972 +/- 0.40, median = 0.9068) pmol mg(-1) albumin. Study participants with high AFB1 levels had significantly lower percentages of CD3+ and CD19+ cells that showed the CD69+ activation marker (CD3+CD69+ and CD19+CD69+) than participants with low AFB1 levels (P = 0.002 for both). Also, the percentages of CD8+ T cells that contained perforin or both perforin and granzyme A were significantly lower in participants with high AFB1 levels compared with those with low AFB1 (P = 0.012 for both). Low levels of CD3+CD69+ (r = -0.32, P = 0.016) and CD19+CD69+ (r = -0.334, P = 0.010) cells were significantly associated with high AFB1 levels using correlation analysis. By multivariate analysis, there were strong negative correlations between the percentages of these cells (CD3+CD69+: b = -0.574, P = 0.001, and CD19+CD69+: b = -0.330, P = 0.032) and AFB1 levels. These alterations in immunological parameters in participants with high AFB1 levels could result in impairments in cellular immunity that could decrease host resistance to infections.
虽然黄曲霉毒素(AFs)已被证明在动物中是免疫抑制剂,但AFs在改变人类白细胞亚群分布和功能方面的潜在作用从未被评估过。我们研究了64名加纳人的细胞免疫状态与血浆中黄曲霉毒素B1(AFB1)-白蛋白加合物水平的关系。使用流式细胞术测量外周血中白细胞免疫表型的百分比、CD4 + T细胞增殖反应、CD4 + T(h)和CD8 + T细胞细胞因子谱以及单核细胞吞噬活性。通过CD3 - CD56 + NK细胞中穿孔素和肿瘤坏死因子-α的表达来确定NK细胞的细胞毒性功能。AFB1 - 白蛋白加合物水平范围为0.3325至2.2703(平均值 = 0.9972 +/- 0.40,中位数 = 0.9068)pmol mg(-1)白蛋白。AFB1水平高的研究参与者显示CD69 +激活标记(CD3 + CD69 +和CD19 + CD69 +)的CD3 +和CD19 +细胞百分比明显低于AFB1水平低的参与者(两者P = 0.002)。此外,与AFB1水平低的参与者相比,AFB1水平高的参与者中含有穿孔素或同时含有穿孔素和颗粒酶A的CD8 + T细胞百分比明显更低(两者P = 0.012)。使用相关分析,低水平的CD3 + CD69 +(r = -0.32,P = 0.016)和CD19 + CD69 +(r = -0.334,P = 0.010)细胞与高AFB1水平显著相关。通过多变量分析,这些细胞(CD3 + CD69 +:b = -0.574,P = 0.001,和CD19 + CD69 +:b = -0.330,P = 0.032)的百分比与AFB1水平之间存在强负相关。AFB1水平高的参与者免疫参数的这些改变可能导致细胞免疫受损,从而降低宿主对感染的抵抗力。