氧化鐵奈米粒子對抗原專一性T細胞免疫及遲發性過敏反應的影響

Abstract

氧化鐵奈米粒子是臨床上使用的核磁共振造影的對比劑。文獻指出氧化鐵奈米粒子會影響免疫細胞的功能，如巨噬細胞、T細胞及樹突細胞等，動物實驗顯示氣管內給予氧化鐵奈米粒子會導致肺臟發炎反應。本研究主旨在探討氧化鐵奈米粒子對抗原專一性T細胞免疫反應的影響。結果顯示靜脈注射一劑氧化鐵奈米粒子 (10-60 mg Fe/kg) 會降低卵白蛋白 (ovalbumin) 致敏小鼠血清中抗原專一性抗體濃度及抑制T細胞的功能。將卵白蛋白致敏的脾臟細胞 (splenocyte) 於離體培養條件下直接暴露氧化鐵奈米粒子 (1-100 μg Fe/mL)，其存活率及介白素-2 (interleukin-2, IL-2) 及介白素-4 (IL-4) 的表現未受影響，但伽馬干擾素 (interferon-γ) 的製造及細胞內谷胱甘肽 (glutathione)的含量受到抑制，且呈現濃度相關性，這些抑制反應可被谷胱甘肽前驅物乙醯基半胱氨酸 (N-acetyl-L-cysteine) 所減緩。此外，靜脈注射一劑氧化鐵奈米粒子 (0.2-10 mg Fe/kg) 亦可抑制遲發性過敏反應，包括腳掌腫脹程度、發炎部位巨嗜細胞及T細胞的浸潤、與介白素-6 (IL-6)、伽馬干擾素及腫瘤壞死因子-α (tumor necrosis factor-α) 的表現量，且脾臟CD11b+細胞之吞噬功能亦有被抑制的情形。上述結果指出氧化鐵奈米粒子可抑制抗原專一性T細胞免疫反應，且藉由抑制第一輔助型T細胞及巨噬細胞的功能，而達到抑制遲發性過敏反應的作用。本論文的結果可提供氧化鐵奈米粒子對抗原專一性體液性及細胞性免疫反應作用之參考依據。

Iron oxide nanoparticles have been used in clinical as a contrasting agent to enhance magnetic resonance imaging. Accumulating evidence indicates that iron oxide nanoparticles modulate the functionality of macrophages, T cells and dendritic cells. Animal studies show that intratracheal administration of iron oxide nanoparticles causes lung inflammation. The objective of the present study is to investigate the potential immune modulatory effect of iron oxide nanoparticles on antigen-specific T cell immunity. The results showed that a single intravenous injection of iron oxide nanoparticles (10-60 mg Fe/kg) attenuated the serum production of antigen-specific antibodies and T cell reactivity in ovalbumin (OVA)-sensitized mice. Direct exposure of OVA-primed splenocytes to iron oxide nanoparticles (1-100 μg Fe/mL) did not affect cell viability and the production of interleukin (IL)-2 and IL-4, whereas the production of interferon (IFN)-γ and intracellular glutathione, was markedly suppressed by iron oxide nanoparticles in a concentration-dependent manner. The effects of iron oxide nanoparticles on IFN-γ and glutathione were attenuated by the presence of N-acetyl-L-cysteine, a precursor of glutathione. Furthermore, intravenous administration of iron oxide nanoparticles (0.2-10 mg Fe/kg), in a dose-dependent fashion, significantly suppressed inflammatory responses associated with delayed-type hypersensitivity (DTH), including the footpad swelling, the infiltration of T cells and macrophages, and the expression of IFN-γ, IL-6 and tumor necrosis factor-α in the inflammatory region. A suppressive effect on the phagocytic activity of splenic CD11b+ cells was also observed. Taken together, the present study demonstrated that iron oxide nanoparticles markedly attenuated antigen-specific T cell immunity and the inhibition of DTH reactions could be mediated by suppressing the functional activity of T helper 1 cells and macrophages. These results provide critical insights into the potential health impact of iron oxide nanoparticles on both humoral and cell-mediated immunity.