Differential effects of interleukin-4 in peptide induced autoimmunity
Differential effects of interleukin-4 in peptide induced autoimmunity
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DOI：
10.1016/s1521-6616(03)00096-2
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发表时间：
2003-08-01
影响因子：
8.6
通讯作者：
Putterman, C
中科院分区：
文献类型：
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作者：
Deocharan, B;Marambio, P;Putterman, C
用多聚体DWEYSVWLSN免疫的BALB/c小鼠产生IgG1抗DNA抗体和肾小球免疫球蛋白沉积，这使我们研究了IL-4在这种抗原诱导的狼疮模型中的作用。DWEYSVWLSN免疫小鼠脾细胞分泌IL-4，但不分泌γ-干扰素。在多肽免疫后，IL-4野生型小鼠的IgG1抗肽和抗DNA抗体水平显著升高，而IL-4基因敲除小鼠的IgM和IgG3抗DNA抗体水平显著升高。IL-4野生型组层粘连蛋白抗体和抗组蛋白抗体的滴度显著高于对照组，而抗Sm/RNP抗体和抗心磷脂抗体的滴度无显著差异。IL-4基因敲除小鼠肾小球免疫球蛋白沉积显著减少。我们的结论是，尽管IL-4不会对与多肽诱导的自身免疫相关的某些自身抗体反应的产生产生实质性的影响，但IL-4缺乏会抑制肾脏免疫球蛋白的沉积。IL-4对狼疮体液自身免疫的影响是复杂的，与遗传背景、抗原触发因素和疾病分期有关。(C)2003年埃尔塞维尔科学公司(美国)。版权所有。
BALB/c mice immunized with multimeric DWEYSVWLSN develop IgG1 anti-DNA antibodies and glomerular immunoglobulin deposits, leading us to investigate the role of IL-4 in this model of antigen induced lupus. Splenocytes from DWEYSVWLSN immunized mice secreted IL-4 but not gamma-interferon. Following peptide immunization, IgG1 anti-peptide and anti-DNA antibodies were significantly higher in IL-4 wild type mice, while IgM and IgG3 anti-DNA levels were significantly higher in IL-4 knockout mice. Titers of IgG anti-laminin and anti-histone, but not anti-Sm/RNP and anti-cardiolipin antibodies, were significantly higher in the IL-4 wild type group. Glomerular immunoglobulin deposition was substantially decreased in IL-4 knockout mice. We conclude that while IL-4 does not materially affect the generation of some autoantibody responses associated with peptide induced autoimmunity, IL-4 deficiency inhibits kidney immunoglobulin deposition. The effect of IL-4 on humoral autoimmunity in lupus is complex, and is dependent on genetic background, the antigenic trigger and stage of disease. (C) 2003 Elsevier Science (USA). All rights reserved.