Objective To study the effect of neonatal immunization with different dosage allergen on the immunity of mice when grown.Methods Fifty neonatal BALB/c mice were divided into 4 groups randomly and subcutaneous injected with different dosage of ovalbumin (OVA) on day 1,8 and 15 after born [NS group(10):injected with saline alone ; NS + AL group(10):injected with saline and AL(OH) 3 ; small dosage (SD) group (15):injected with 10 μg OVA and AL (OH) 3 ; large dosage (LD) group (15):injected with 1000 μg OVA and AL(OH)3].The mice were then challenged using caudal vein injection on 5 weeks old (NS group and NS + AL group were challenged with saline,SD group and LD group were challenged with 100 μg OVA).The blood was collected 1 week later to examine OVA specific IgE,IgG1 and IgG2a.Mononuclear cells were drawn from the spleen and cultured.Concentration of IL-4,IFN-r,IL-10 was examined in the cultural supernatant.Flow cytometry was used to test the expression of CD4 + IL-4 +,CD4 + IFN-γ+,CD4 + IL-10 + cells.Results It was found that concentration of OVA specific IgE (OVA-sIgE) in SD group (0.33 ± 0.18) was significantly higher than that of NS (0.07 ± 0.01) and NS + AL (0.09±0.04) group (t value was-3.46 and-3.21,all P＜0.01),and LD group (0.17 ±0.10) as well (t =2.58,P ＜0.05).The concentration of OVA-sIgE was higher in LD group than that of NS group (t=-2.53,P＜0.05),but similar with that of NS +AL group (t =-2.04,P ＞0.05).Both the concentration of OVA-sIgG1 and sIgG2a was higher in SD and LD group than that of NS and NS + AL group (all P ＜ 0.05).The concentration of IL-4,IFN-γ and IL-10 in the cultural supernatant of spleen mononuclear was all higher in SD group than that of NS and NS + AL group (all P ＜ 0.01).The ratio of IFN-γ/IL-4 was significantly lower in SD group than that of NS and NS + AL group (t value was 2.14,3.44,all P ＜ 0.05),while the same ratio was higher in LD group than that of NS and NS + AL group (t value was-2.14,-1.61,all P ＜0.05).Ratio of CD4+ IL-4+ cells was significant lower in LD group than that of SD group (P ＜ 0.05),while it was not different with that of NS and NS + AL group (P ＞ 0.05).Conclusion Neonatal immunization with low dosage OVA could generate a specific immunity with Th2 direction,while with large dosage OVA could generate a specific immunity with Th1 direction.%目的 研究小鼠生命早期不同剂量变应原免疫干预对将来免疫功能状态的影响.方法 50只新生小鼠分完全随机为4组,出生后第1、8、15天给予不同剂量卵清蛋白(ovalbumin,OVA)或生理盐水及佐剂皮下注射.NS组:10只,皮下注射生理盐水；NS+ AL组:10只,皮下注射生理盐水+ Al(OH)3；小剂量组:15只,皮下注射10 μg OVA +AL(OH)3;大剂量组:15只,皮下注射1000 μg OVA +Al(OH)3.5周龄时尾静脉注射激发,其中NS组及NS+ AL组给予生理盐水激发,小剂量组及大剂量组予100 μg OVA激发,1周后收集血清,检测OVA特异性IgE、IgG1及IgG2a含量.行脾单个核细胞培养后检测上清中白细胞介素(interleukin,IL)4、γ干扰素(interferon,IFN-γ)、IL-10水平.流式细胞术检测脾单个核细胞中CD4+ IL4+、CD4+ IFN-γ+、CD4+ IL-10+细胞表达情况.结果 小剂量组血清OVA特异性IgE为(0.33 ±0.18),高于NS组的(0.07 ±0.01)、NS+ AL组的(0.09 ±0.04)、以及大剂量组的(0.17±0.10),差异有统计学意义(t值分别为-3.46、-3.21、2.58,P值分别＜0.01,＜0.01,＜0.05).大剂量组OVA-IgE高于NS组(t=-2.53,P＜0.05)但与NS+ AL组间差异无统计学意义(t=-2.04,P＞0.05).小剂量组及大剂量组OVA特异性IgG1及IgG2a均高于NS及NS+ AL组(P值均＜0.05).脾细胞培养细胞因子检测结果显示,小剂量组IL-4、IFN-γ及IL-10均高于NS及NS+ AL组(P值均＜0.01).但小剂量组IFN-γ/IL-4比值低于NS及NS+ AL组(t值分别为2.14、3.44,P值均＜0.05),而大剂量组IFN-γ/IL-4比值高于NS及NS+ AL组(t值分别为-2.14、-1.61,P值均＜0.05).流式检测结果表明,大剂量组CD4+ IL-4+细胞较小剂量组明显减少(P＜0.05),与NS组及NS+ AL组差异无统计学意义(P＞0.05).结论 生命早期小剂量OVA干预,可使小鼠机体形成Th2方向为主导的特异性免疫反应；而大剂量OVA干预时,则可使其形成Th1方向为主导的特异性免疫反应.
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