Species specialization in cytokine biology: Is interleukin-4 central to the TH1-TH2 paradigm in swine?
Species specialization in cytokine biology: Is interleukin-4 central to the TH1-TH2 paradigm in swine?
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DOI：
10.1016/j.dci.2008.06.014
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发表时间：
2009-01-01
影响因子：
2.9
通讯作者：
Zhou, Yaling
中科院分区：
文献类型：
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作者：
Murtaugh, Michael P.;Johnson, Craig R.;Zhou, Yaling
T(H)1-T(H)2范式提供了一种针对感染性病原体的定向反应的优雅模型。该模型在小鼠中开发，为猪免疫调节、保护性免疫和疫苗开发的系统和机制研究提供了框架。白细胞介素-4 （IL-4）作为一种调控分子在T(H)2表型的发展中起着核心作用，作为抗体产生所必需的发育细胞因子，作为T(H)2细胞类型的可溶性诊断标记物。相比之下，在表征猪IL-4的生物学特性时，我们发现它不是猪B细胞的刺激因子。相反，它阻断抗体和IL-6的分泌，抑制抗原刺激的B细胞增殖。IL-2和IL-6的抑制作用未被逆转。IL-4不刺激T淋巴细胞增殖，但以剂量依赖性方式诱导淋巴母细胞生长。这些结果表明，IL-4在猪身上的作用与在小鼠和人类身上的作用不同，它刺激B细胞，对抗体的产生至关重要。此外，IL-4在猪体内的功能不能从小鼠等模型系统的结果中推断出来。一般的抗病模型显示猪和老鼠在细胞和分子水平上有很大的差异。体细胞技术和动物工程的进步使猪的基因敲除成为可能，再加上不断扩大的免疫学工具包，猪免疫学的前景令人兴奋，T(H)1-T(H)2范式的详细机制阐明，以及对IL-4在猪对传染病免疫中的作用的进一步了解。(c) 2008 Elsevier Ltd.版权所有。
The T(H)1-T(H)2 paradigm provides an elegant model of directed response to infectious pathogens. Developed in the mouse, the model has provided a framework for systematic and mechanistic studies of immune regulation, protective immunity, and vaccine development in swine. Interleukin-4 (IL-4) plays a central role in the paradigm as a regulatory molecule directing development of the T(H)2 phenotype, as a developmental cytokine essential for antibody production, and as a soluble diagnostic marker of the T(H)2 cell type. In contrast, while characterizing the biological properties of porcine IL-4, we discovered that it was not a stimulatory factor for porcine B cells. Rather, it blocked antibody and IL-6 secretion and suppressed antigen-stimulated proliferation of B cells. Inhibition was not reversed by treatment with IL-2 and IL-6 treatment. IL-4 did not stimulate T lymphocyte proliferation, but induced cell growth in lymphoblasts in a dose-dependent fashion. These results suggest that IL-4 plays a different role in pigs than in mice and humans, in which it stimulates B cells and is essential for antibody production. Furthermore, the functions of IL-4 in swine cannot be inferred from results in model systems such as the mouse. General models of disease resistance show substantial variation between pigs and mice at the cellular and molecular level. Advances in somatic cell technologies and animal engineering to enable gene knockouts in pigs, in combination with a continuously expanding immunological toolkit, promise an exciting future for pig immunology, detailed mechanistic elucidation of the T(H)1-T(H)2 paradigm, and an improved understanding of the role of IL-4 in porcine immunity to infectious disease. (c) 2008 Elsevier Ltd. All rights reserved.