Saloga J, Renz H, Lack G, Bradley K L, Greenstein J L, Larsen G, Gelfand E W
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
J Clin Invest. 1993 Jan;91(1):133-40. doi: 10.1172/JCI116162.
We previously showed that BALB/c mice sensitized to ovalbumin (OVA) by brief daily inhalations of antigen over 10 consecutive days exhibit elevated antigen-specific serum IgE antibody levels and increased airways responsiveness. For the first time, we now show that animals sensitized in this fashion to either OVA or ragweed (RGW) develop immediate hypersensitivity skin test reactions when challenged 2 d after completion of the sensitization protocol. Skin testing, performed by direct assessment of wheal formation after intradermal injection of allergen, was sensitive and specific, since animals exposed to RGW by inhalation only responded to RGW, and OVA-sensitized animals responded only to OVA. Positive reactions were associated with mast cell degranulation, whereas control injections were not. Since only sensitized IgE high responder BALB/c mice but neither nonsensitized BALB/c mice nor OVA-sensitized IgE low responder SJL/J mice exhibited wheal responses, induction of OVA-specific IgE appeared to be essential for the mediation of OVA-specific immediate hypersensitivity reactions of the skin in this model. Passive cutaneous anaphylaxis (PCA) testing confirmed the presence of antigen-specific IgE in the serum. Mice that developed IgG (predominantly IgG2b) anti-OVA antibodies did not respond to OVA injection, indicating that OVA-specific IgG was not involved in this system. Further support for the role of IgE in the immediate hypersensitivity response included the wheal response to intradermal injection of anti-IgE antibody that occurred in OVA- and RGW-sensitized mice at 10-fold lower concentrations than in nonsensitized BALB/c mice and not in sensitized SJL/J mice. After transfer of mononuclear cells from peribronchial lymph nodes of OVA- or RGW-sensitized BALB/c mice, naive, syngeneic recipients developed antigen-specific IgE and specific immediate hypersensitivity responses, indicating that the local lymphoid tissue at the site of sensitization can transfer responsiveness to these allergens. These results demonstrate for the first time the ability to elicit and study IgE-mediated immediate skin hypersensitivity responses in the mouse and illustrate the association of increased antigen-specific and total serum IgE levels, airways hyperresponsiveness, and antigen-specific immediate cutaneous reactivity after sensitization to allergen via the airways.
我们之前的研究表明，连续10天每天短暂吸入抗原使BALB/c小鼠对卵清蛋白（OVA）致敏后，其抗原特异性血清IgE抗体水平升高，气道反应性增强。现在我们首次发现，以这种方式对OVA或豚草（RGW）致敏的动物，在致敏方案完成后2天受到攻击时会出现速发型超敏皮肤试验反应。通过皮内注射变应原后直接评估风团形成进行的皮肤试验敏感且特异，因为仅通过吸入接触RGW的动物仅对RGW有反应，而OVA致敏的动物仅对OVA有反应。阳性反应与肥大细胞脱颗粒相关，而对照注射则无此现象。由于只有致敏的IgE高反应性BALB/c小鼠出现风团反应，未致敏的BALB/c小鼠和OVA致敏的IgE低反应性SJL/J小鼠均未出现，因此在该模型中，OVA特异性IgE的诱导似乎是介导皮肤OVA特异性速发型超敏反应所必需的。被动皮肤过敏反应（PCA）试验证实血清中存在抗原特异性IgE。产生IgG（主要是IgG2b）抗OVA抗体的小鼠对OVA注射无反应，表明OVA特异性IgG不参与该系统。IgE在速发型超敏反应中作用的进一步证据包括，OVA和RGW致敏小鼠对皮内注射抗IgE抗体的风团反应，其所需浓度比未致敏的BALB/c小鼠低10倍，而致敏的SJL/J小鼠则无此反应。将OVA或RGW致敏的BALB/c小鼠支气管周围淋巴结的单核细胞转移后，同基因的未致敏受体产生了抗原特异性IgE和特异性速发型超敏反应，这表明致敏部位的局部淋巴组织可传递对这些变应原的反应性。这些结果首次证明了在小鼠中引发和研究IgE介导的速发型皮肤超敏反应的能力，并说明了通过气道致敏变应原后，抗原特异性和总血清IgE水平升高、气道高反应性以及抗原特异性速发型皮肤反应性之间的关联。
