Yasue M, Yokota T, Fukada M, Takai T, Suko M, Okudaira H, Okumura Y
Bioscience Research and Development Laboratory, Asahi Breweries Ltd, Ibaraki, Japan.
Clin Exp Immunol. 1998 Jul;113(1):1-9. doi: 10.1046/j.1365-2249.1998.00616.x.
C8/119S is a mutant of recombinant Der f 2 (rDer f 2), and lacks a disulphide bond possessed by wild-type rDer f 2. In humans and mice, C8/119S has a very weak IgE-binding capacity compared with the wild-type, but possesses a T cell reactivity comparable to that of the wild-type. C8/119S may thus be a safe immunotherapeutic agent for house dust mite allergy. The aim of the present study was to evaluate whether the intranasal administration of C8/119S could suppress an immediate allergic reaction in mice sensitized with wild-type rDer f 2, possessing an allergic activity comparable to native counterparts purified from mite extract. Seven-week-old male A/J mice were immunized with wild-type rDer f 2 four times, and then intranasally administered 0.2-2 microg of wild-type, 0.2-20 microg of C8/119S, or PBS alone, three times a week for 4 weeks. Seven days after the last administration, the mice were examined for an immediate allergic reaction. The animals administered 2 microg of C8/119S (C2.0 group) showed significantly reduced immediate bronchoconstriction provoked by the i.v. injection of 1 and 10 microg of wild-type rDer f 2, compared with the PBS-treated mice. Similar results were obtained when we examined mice 10 weeks after the last administration. The reactions in the other groups given wild-type or C8/119S also tended to decrease in severity in comparison with the animals of the PBS group. The allergic phenotypes of the T cells, B cells, and basophils in the C2.0 group were shifted to that of naive mice without immunization. We conclude that C8/119S has hyposensitizing activities in mice sensitized with wild-type rDer f 2. C8/119S may be useful for immunotherapy of house dust mite allergy.
C8/119S是重组Der f 2（rDer f 2）的一种突变体，缺少野生型rDer f 2所具有的一个二硫键。在人类和小鼠中，与野生型相比，C8/119S的IgE结合能力非常弱，但具有与野生型相当的T细胞反应性。因此，C8/119S可能是一种用于治疗屋尘螨过敏的安全免疫治疗剂。本研究的目的是评估鼻内给予C8/119S是否能抑制用野生型rDer f 2致敏的小鼠的速发型过敏反应，野生型rDer f 2具有与从螨提取物中纯化的天然对应物相当的过敏活性。7周龄雄性A/J小鼠用野生型rDer f 2免疫4次，然后鼻内给予0.2 - 2微克野生型、0.2 - 20微克C8/119S或仅给予PBS，每周3次，共4周。最后一次给药7天后，检查小鼠的速发型过敏反应。与PBS处理的小鼠相比，给予2微克C8/119S的动物（C2.0组）在静脉注射1微克和10微克野生型rDer f 2时引发的速发型支气管收缩明显减轻。在最后一次给药10周后检查小鼠时也获得了类似结果。与PBS组动物相比，给予野生型或C8/119S的其他组的反应严重程度也有降低趋势。C2.0组中T细胞、B细胞和嗜碱性粒细胞的过敏表型转变为未免疫的幼稚小鼠的表型。我们得出结论，C8/119S在用野生型rDer f 2致敏的小鼠中具有脱敏活性。C8/119S可能对屋尘螨过敏的免疫治疗有用。
