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舌下给予天然或变性蛋白过敏原与佐剂CpG寡脱氧核苷酸或霍乱毒素对小鼠全身Th2免疫反应和黏膜免疫的影响。

Effect of sublingual administration with a native or denatured protein allergen and adjuvant CpG oligodeoxynucleotides or cholera toxin on systemic T(H)2 immune responses and mucosal immunity in mice.

作者信息

Huang Ching-Feng, Wang Chih-Chien, Wu Tzee-Chung, Chu Chia-Hsiang, Peng Ho-Jen

机构信息

Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.

出版信息

Ann Allergy Asthma Immunol. 2007 Nov;99(5):443-52. doi: 10.1016/S1081-1206(10)60570-4.

Abstract

BACKGROUND

Sublingual immunotherapy has been recently used for allergic diseases, but its mechanisms are still unclear.

OBJECTIVE

To examine the effect of sublingual administration of a native or denatured allergen alone or plus adjuvant on systemic T(H)2 responses and mucosal immunity in mice.

METHODS

Naive or sensitized BALB/c mice were sublingually vaccinated biweekly for 3 weeks with ovalbumin (OVA) or urea-denatured OVA (CM-OVA) only or plus adjuvant CpG oligodeoxynucleotides (CpG) or cholera toxin (CT). Two weeks later, their specific serum IgG, IgG1, IgG2a, IgE, and saliva secretory IgA (SIgA) antibody responses and the cytokine profiles of spleen and cervical lymph node cells were investigated.

RESULTS

Specific SIgA antibody responses were induced by vaccination with CM-OVA plus CpG or CT. Whereas vaccination with CM-OVA and CpG enhanced T(H)1 responses but inhibited IgE production, vaccination with CT and CM-OVA or OVA increased cervical lymph node cell production of interleukin (IL) 4, IL-5, and IL-6 and serum IgG1 antibody responses. In previously sensitized mice, sublingual vaccination with OVA or CM-OVA plus CT or CpG stimulated mucosal SIgA antibody responses, but did not enhance ongoing IgE antibody responses.

CONCLUSIONS

Sublingual vaccination with OVA or CM-OVA plus adjuvant CT or CpG all can induce systemic and mucosal immunity, but CM-OVA plus CpG had the best prophylactic and therapeutic effects on IgE antibody production. It is likely that sublingual vaccines may have a role for the prophylaxis and immunotherapy of allergic reactions.

摘要

背景

舌下免疫疗法最近已用于治疗过敏性疾病,但其机制仍不清楚。

目的

研究单独或联合佐剂舌下给予天然或变性变应原对小鼠全身T(H)2反应和黏膜免疫的影响。

方法

将未致敏或已致敏的BALB/c小鼠每两周舌下接种一次,共3周,分别接种卵清蛋白(OVA)、尿素变性OVA(CM-OVA),或联合佐剂CpG寡脱氧核苷酸(CpG)或霍乱毒素(CT)。两周后,检测其特异性血清IgG、IgG1、IgG2a、IgE和唾液分泌型IgA(SIgA)抗体反应,以及脾脏和颈部淋巴结细胞的细胞因子谱。

结果

接种CM-OVA联合CpG或CT可诱导特异性SIgA抗体反应。接种CM-OVA和CpG可增强T(H)1反应,但抑制IgE产生;接种CT与CM-OVA或OVA可增加颈部淋巴结细胞白细胞介素(IL)4、IL-5和IL-6的产生以及血清IgG1抗体反应。在预先致敏的小鼠中,舌下接种OVA或CM-OVA联合CT或CpG可刺激黏膜SIgA抗体反应,但不增强正在进行的IgE抗体反应。

结论

舌下接种OVA或CM-OVA联合佐剂CT或CpG均可诱导全身和黏膜免疫,但CM-OVA联合CpG对IgE抗体产生具有最佳的预防和治疗效果。舌下疫苗可能在预防和免疫治疗过敏反应中发挥作用。

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