Kim Hyon-Jeen, Barajas Berenice, Chan Ray Chun-Fai, Nel Andre E
Department of Medicine, Division of Clinical Immunology and Allergy, University of California, Los Angeles, CA 90095, USA.
J Allergy Clin Immunol. 2007 May;119(5):1225-33. doi: 10.1016/j.jaci.2007.01.016. Epub 2007 Mar 1.
Dendritic cells (DCs) play a key role as antigen-presenting cells in the immune system. There is growing evidence that the redox equilibrium of these cells influences their ability to induce T-cell activation and to regulate the polarity of the immune response. This could affect the outcome of the immune response during systemic diseases and aging.
Our aim was to elucidate the mechanism by which the redox equilibrium of antigen-presenting DCs affects the delayed-type hypersensitivity (DTH) response during experimental modification of glutathione levels, as well as during aging.
We looked at the effect of glutathione depletion by diethyl maleate in DCs as well as during systemic administration on the DTH response to the contact-sensitizing antigens, oxazolone, and 2,4-dinitro-1-fluorobenzene. We also determined whether glutathione repletion with N-acetyl cysteine could influence the decline of the DTH response in aged mice.
Glutathione depletion in bone marrow-derived DCs interfered in their ability to mount a DTH response on adoptive transfer into recipient mice. Glutathione depletion interfered in IL-12 production and costimulatory receptor expression in DCs, leading to decreased IFN-gamma production in the skin of recipient mice. Systemic diethyl maleate treatment exerted similar effects on the DTH response and IFN-gamma production, whereas N-acetyl cysteine administration reversed the decline of the DTH response in aged animals.
Glutathione depletion downregulates T(H)1 immunity through a perturbation of DC maturation and IL-12 production.
These data show that the induction of oxidative stress in the immune system, under disease conditions and aging, interferes in T(H)1 immunity.
树突状细胞（DCs）作为免疫系统中的抗原呈递细胞发挥着关键作用。越来越多的证据表明，这些细胞的氧化还原平衡会影响其诱导T细胞活化以及调节免疫反应极性的能力。这可能会影响全身性疾病和衰老过程中免疫反应的结果。
我们的目的是阐明在实验性改变谷胱甘肽水平以及衰老过程中，抗原呈递DCs的氧化还原平衡影响迟发型超敏反应（DTH）的机制。
我们研究了马来酸二乙酯对DCs以及全身给药时谷胱甘肽耗竭对接触性致敏抗原恶唑酮和2,4-二硝基-1-氟苯的DTH反应的影响。我们还确定了用N-乙酰半胱氨酸补充谷胱甘肽是否会影响老年小鼠DTH反应的下降。
骨髓来源的DCs中的谷胱甘肽耗竭干扰了它们在过继转移到受体小鼠后引发DTH反应的能力。谷胱甘肽耗竭干扰了DCs中IL-12的产生和共刺激受体的表达，导致受体小鼠皮肤中IFN-γ产生减少。全身马来酸二乙酯治疗对DTH反应和IFN-γ产生产生类似影响，而给予N-乙酰半胱氨酸可逆转老年动物DTH反应的下降。
谷胱甘肽耗竭通过干扰DC成熟和IL-12产生来下调T（H）1免疫。
这些数据表明，在疾病状态和衰老情况下，免疫系统中氧化应激的诱导会干扰T（H）1免疫。
