Interleukin 4 expressed in situ selectively alters thymocyte development.
Interleukin 4 expressed in situ selectively alters thymocyte development.
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DOI：
10.1084/jem.173.1.89
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发表时间：
1991-01-01
期刊：
影响因子：
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通讯作者：
Perlmutter RM
中科院分区：
文献类型：
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作者：
Lewis DB;Yu CC;Forbush KA;Carpenter J;Sato TA;Grossman A;Liggitt DH;Perlmutter RM
利用转基因小鼠模型，我们发现胸腺内白介素4(IL-4)的表达增加显着干扰胸腺细胞的发育。转基因双阳性(CD4+CD8+)胸腺细胞数量显著减少，表现出T细胞受体(TCR)表达增加，并由这些受体介导的钙动员增加。相比之下，转基因单阳性(CD4+CD8-和CD4-CD8+)胸腺细胞和外周T细胞表现出TCR介导的钙动员减少。体内表达的IL-4显著干扰了CD4-CD8+胸腺细胞的发育；在转基因小鼠中只发现了大量的外周CD4+T细胞，而CD4-CD8+胸腺细胞的数量增加，显然是因为它们未能迁移到外周。与这些对T细胞发育的选择性作用相反，转基因小鼠和对照小鼠在B细胞或肥大细胞数量、血浆IgE和IgG1水平方面没有显著差异。这些观察表明，IL-4在体内的主要作用是局部的，而不是全身的，即使它的表达是结构性增加的。
Using a transgenic mouse model we show that increased intrathymic expression of interleukin 4 (IL-4) significantly perturbs the development of thymocytes. Transgenic double-positive (CD4+CD8+) thymocytes, which are present in dramatically reduced numbers, exhibit increased T cell receptor (TCR) expression and increased mobilization of calcium mediated by these receptors. In contrast, transgenic single- positive (CD4+CD8- and CD4-CD8+) thymocytes and peripheral T cells exhibit decreased TCR-mediated calcium mobilization. The development of CD4-CD8+ thymocytes is significantly perturbed by IL-4 expressed in vivo; only peripheral CD4+ T cells are found in significant numbers in transgenic mice, while CD4-CD8+ thymocytes are present in increased numbers, apparently because of their failure to emigrate to the periphery. In contrast to these selective effects on T cell development, no significant differences in the numbers of B cells or mast cells, or in the plasma levels of IgE and IgG1 are observed between transgenic and control mice. These observations suggest that IL- 4 in vivo exerts its major effects locally rather than systemically, even when its expression is constitutively increased.