Interleukin-4 receptor alpha-deficient BALB/c mice show an unimpaired T helper 2 polarization in response to Leishmania major infection
Interleukin-4 receptor alpha-deficient BALB/c mice show an unimpaired T helper 2 polarization in response to Leishmania major infection
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DOI：
10.1128/iai.68.4.1773-1780.2000
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发表时间：
2000-04-01
影响因子：
3.1
通讯作者：
Brombacher, F
中科院分区：
文献类型：
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作者：
Mohrs, M;Holscher, C;Brombacher, F
最近，我们产生了白细胞介素-4（IL-4）受体α缺陷（IL-4 R α（-/-））BALB/c小鼠，并显示了IL-13介导的功能在利什曼病中的保护作用的证据。在这项研究中，我们研究了IL-4表达和辅助性T细胞2（Th 2）的发展在利什曼原虫感染IL-4 R α（-/-）小鼠。在这里，我们发现在L.主要感染的BALB/c小鼠不依赖于IL-4 R α介导的功能。随后，我们证实了体外Th 2发育受损。主要感染后，分离的CD 4（+）IL-4 R α（-/-）T细胞表达高IL-4-但低γ干扰素（IFN-γ）特异性mRNA，与Th 2极化的BALB/c CD 4（+）细胞相当，与Th 1极化的C57 BL/6 CD 4（+）细胞相反。由于IL-4 R α（-/-）小鼠的抗原特异性再刺激的腘淋巴结细胞（PLN）也以高IL-4但低IFN-γ产生应答，与野生型BALB/c小鼠的Th 2极化细胞相当，与Th 1极化的C57 BL/6细胞相反，这些结果表明在建立的L.为了进一步确定观察到的IL-4受体非依赖性Th 2细胞表型，我们确定了一种独立的Th 2标志物，即CD 4（+）T细胞的IL-12受体β-2（IL-12 R β 2）特异性转录水平。在L.主要感染的IL-4 R α（-/-）小鼠，发现来自感染的IL-4 R α（-/-）小鼠的CD 4（+）T细胞和来自BALB/c小鼠的Th 2细胞之间的IL-12 R β 2信使水平相当，而Th 1极化的C57 BL/6细胞显示显著增加的IL-12 R β 2表达水平，这些结果表明，IL-4 R α介导的信号不是诱导和维持L.主要感染BALB/c小鼠，并表明IL-4 R α非依赖性机制是L.主要感染BALB/c小鼠。
We recently generated interleukin-4 (IL-4) receptor alpha-deficient (IL-4R alpha(-/-)) BALB/c mice and showed evidence for a protective role of IL-13-mediated functions in leishmaniasis, In this study, we investigated the IL-4 expression and T helper 2 (Th2) development in Leishmania major-infected IL-4R alpha(-/-) mice. Here we show that the early burst of IL-4 expression observed in L. major-infected BALB/c mice is independent of IL-4R alpha-mediated functions. Subsequently, we confirmed an impaired Th2 development in vitro, Unexpectedly, during L. major infection, isolated CD4(+) IL-4R alpha(-/-) T cells expressed high IL-4- but low gamma interferon (IFN-gamma) specific mRNA, comparable to Th2-polarized BALB/c CD4(+) cells and in contrast to Th1-polarized C57BL/6 CD4(+) cells. Since antigen-specific restimulated popliteal lymph node cells (PLN) of IL-4R alpha(-/-) mice also responded with high IL-4 but low IFN-gamma production, comparable to Th2-polarized cells from wild-type BALB/c mice and in contrast to Th1-polarized C57BL/6 cells, these results suggested an unimpaired Th2 polarization during an established infection with L. major, To further define the observed IL-4 receptor independent Th2 cell phenotype, we determined an independent Th2 marker, the IL-12 receptor beta-2 (IL-12R beta 2)-specific transcript levels of CD4(+) T cells. Confirming Th2 polarization in L. major-infected IL-4R alpha(-/-) mice, comparable IL-12R beta 2 message levels between CD4(+) T cells from infected IL-4R alpha(-/-) mice and Th2 cells from BALB/c mice were found, whereas Th1-polarized C57BL/6 cells showed strikingly increased IL-12R beta 2 expression levels, These results indicate that signals mediated by the IL-4R alpha are not necessary to induce and sustain an efficient IL-4 expression and Th2 polarization in L. major-infected BALB/c mice and suggest that IL-4R alpha-independent mechanisms underlie the default Th2 development in L. major-infected BALB/c mice.