Matsumoto M, Itakura A, Tanaka A, Fujisawa C, Matsuda H
Laboratory of Clinical Immunology, Department of Veterinary Clinic, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.
J Immunol. 2001 Nov 15;167(10):5955-62. doi: 10.4049/jimmunol.167.10.5955.
NC/Nga mice raised in nonsterile circumstances spontaneously suffer from atopic dermatitis-like skin lesions with IgE hyperproduction. We investigated effects of rIL-12 on the IgE production in NC/Nga mice. rIL-12 administration was successful to suppress the increase of IgE levels in BALB/c mice immunized with OVA and aluminum hydroxide, but failed to abrogate that in NC/Nga mice. Both in vivo and in vitro IFN-gamma production induced by rIL-12 was less in NC/Nga mice than in BALB/c mice. Addition of rIFN-gamma to rIL-4 and LPS completely abrogated IgE production by B cells of BALB/c mice, but was insufficient to suppress it by B cells of NC/Nga mice. In splenic cells pretreated with Con A, STAT4 was phosphorylated at the tyrosine residue by addition of rIL-12, which was more weakly inducible in NC/Nga mice than in BALB/c mice. Finally, we examined the preventive ability of rIL-12 on the clinical aspects of atopic dermatitis in NC/Nga mice. rIL-12 administration resulted in exacerbation of development of the skin lesions and IgE production in NC/Nga mice raised in nonsterile circumstances. These results suggest that defective production of IFN-gamma by T cells less sensitive to IL-12 and low responsiveness of B cells to IFN-gamma may contribute to IgE hyperproduction in NC/Nga mice, and that IL-12 may have no ability to improve the clinical aspects of NC/Nga mice.
在非无菌环境中饲养的NC/Nga小鼠会自发患上类似特应性皮炎的皮肤损伤，并伴有IgE过度产生。我们研究了重组白细胞介素-12（rIL-12）对NC/Nga小鼠中IgE产生的影响。给予rIL-12成功抑制了用卵清蛋白（OVA）和氢氧化铝免疫的BALB/c小鼠中IgE水平的升高，但未能消除NC/Nga小鼠中的这种升高。rIL-12诱导的体内和体外γ干扰素（IFN-γ）产生在NC/Nga小鼠中比在BALB/c小鼠中少。向rIL-4和脂多糖（LPS）中添加rIFN-γ完全消除了BALB/c小鼠B细胞产生的IgE，但不足以抑制NC/Nga小鼠B细胞产生的IgE。在用刀豆蛋白A（Con A）预处理的脾细胞中，添加rIL-12可使信号转导和转录激活因子4（STAT4）在酪氨酸残基处磷酸化，这在NC/Nga小鼠中的诱导作用比在BALB/c小鼠中更弱。最后，我们研究了rIL-12对NC/Nga小鼠特应性皮炎临床症状的预防能力。给予rIL-12导致在非无菌环境中饲养的NC/Nga小鼠的皮肤损伤发展和IgE产生加剧。这些结果表明，对IL-12敏感性较低的T细胞产生IFN-γ存在缺陷以及B细胞对IFN-γ反应性较低可能导致NC/Nga小鼠中IgE过度产生，并且IL-12可能无法改善NC/Nga小鼠的临床症状。
