Mechanisms for induction of acquired host immunity by neutrophil peptide defensins
Mechanisms for induction of acquired host immunity by neutrophil peptide defensins
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DOI：
10.1073/pnas.96.2.651
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发表时间：
1999-01-19
影响因子：
11.1
通讯作者：
McGhee, JR
中科院分区：
文献类型：
--
作者：
Lillard, JW;Boyaka, PN;McGhee, JR
研究了人中性粒细胞肽（HNP）防御素在适应性粘膜免疫中的潜在作用。经鼻给药HNPs加卵清蛋白（OVA）可增强OVA特异性血清IgG抗体（Ab）反应。然而，ova特异性IgA抗体在粘膜分泌物或血清中未被诱导。与单独接受OVA的对照组相比，鼻内免疫小鼠的CD4(+) T细胞表现出更高的OVA特异性增殖反应，干扰素γ、白细胞介素（IL） 5、IL-6和IL-10的产生升高。在体外，HNPs还增强了CD3 epsilon刺激的脾脏和Peyer's贴片来源的初始CD4(+) T细胞的增殖反应和T辅助（Th）细胞因子分泌谱。HNPs分别通过脂多糖或CD3 epsilon刺激脾脏和Peyer’s斑块B或T细胞群调节共刺激分子的表达。这些研究表明，防御素通过CD4(+) Th1-和th2型细胞因子的帮助，增强全身IgG应答，而不是IgA、Ab应答，并促进B细胞和T细胞相互作用，将先天免疫与适应性免疫系统联系起来。
Human neutrophil peptide (HNP) defensins were studied to determine their potential effects on adaptive mucosal immunity. Intranasal delivery of HNPs plus ovalbumin (OVA) enhanced OVA-specific serum IgG antibody (Ab) responses. However, OVA-specific IgA Abs were not induced in mucosal secretions or in serum. CD4(+) T cells of intranasally immunized mice displayed higher OVA-specific proliferative responses and elevated production of interferon gamma, interleukin (IL) 5, IL-6, and IL-10 when compared with control groups receiving OVA alone. In vitro, HNPs also enhanced both proliferative responses and T helper (Th) cytokine secretion profiles of CD3 epsilon-stimulated spleen- and Peyer's patch-derived naive CD4(+) T cells. HNPs modulated the expression of costimulatory molecules by lipopolysaccharide- or CD3 epsilon-stimulated splenic and Peyer's patch B or T cell populations, respectively. These studies show that defensins enhance systemic IgG, but not IgA, Ab responses through help provided by CD4(+) Th1- and Th2-type cytokines and foster B and T cell interactions to link innate immunity with the adaptive immune system.