Mouse Vα14i natural killer T cells are resistant to cytokine polarization in vivo
Mouse Vα14i natural killer T cells are resistant to cytokine polarization in vivo
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DOI：
10.1073/pnas.1332805100
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发表时间：
2003-07-08
影响因子：
11.1
通讯作者：
Kronenberg, M
中科院分区：
文献类型：
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作者：
Matsuda, JL;Gapin, L;Kronenberg, M
在不同的情况下，自然杀伤T（NKT）细胞可以引起辅助性T细胞（Th）1或Th 2极化的免疫反应。然而，我们在这里显示，具有不变的Valpha 14重排的小鼠NKT细胞（Valpha 14 i NKT细胞）快速产生IL-4和IFN-γ，并且这种模式不能通过抑制幼稚CD 4（+）T细胞的方法改变。令人惊讶的是，尽管仅在活化后检测到细胞因子蛋白，但静息的Valpha 14 i NKT细胞含有IL-4和IFN-γ mRNA。尽管有这一发现，在体内用Valpha 14 i NKT细胞识别的糖脂抗原致敏的小鼠在抗原再暴露后导致更多的Th 2-导向应答。来自致敏小鼠的Valpha 14 i NKT细胞保留了产生IL-4和IFN-γ的能力，但它们在激活NK细胞以产生IFN-γ方面不太有效。因此，我们的数据表明，Valpha 24 i NKT细胞具有相对不灵活的立即细胞因子应答，但是它们诱导NK细胞分泌IFN-γ的能力的变化可能决定它们促进Th 1应答的程度。
Under different circumstances, natural killer T (NKT) cells can cause a T helper (Th) 1 or a Th2 polarization of immune responses. We show here, however, that mouse NKT cells with an invariant Valpha14 rearrangement (Valpha14i NKT cells) rapidly produce both IL-4 and IFN-gamma, and this pattern could not be altered by methods that polarize naive CD4(+) T cells. Surprisingly, although cytokine protein was detected only after activation, resting Valpha14i NKT cells contained IL-4 and IFN-gamma mRNAs. Despite this finding, in vivo priming of mice with the glycolipid antigen recognized by Valpha14i NKT cells resulted in a more Th2-oriented response upon antigen re-exposure. The Valpha14i NKT cells from primed mice retain the ability to produce IL-4 and IFN-gamma, but they are less effective at activating NK cells to produce IFN-gamma. Our data therefore indicate that Valpha24i NKT cells have a relatively inflexible immediate cytokine response, but that changes in their ability to induce IFN-gamma secretion by NK cells may determine the extent to which they promote Th1 responses.