Production of IFN-γ by CD4+ T cells in response to malaria antigens is IL-2 dependent
Production of IFN-γ by CD4+ T cells in response to malaria antigens is IL-2 dependent
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DOI：
10.1093/intimm/dxq448
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发表时间：
2010-12-01
影响因子：
4.4
通讯作者：
Yui, Katsuyuki
中科院分区：
文献类型：
--
作者：
Kimura, Daisuke;Miyakoda, Mana;Yui, Katsuyuki
T细胞免疫应答对于保护宿主和在疟原虫属物种感染期间的疾病发病机制至关重要。我们研究了伯氏疟原虫ANKA（PbA）感染过程中CD 4（+）T细胞细胞因子反应的调节。来自PbA感染小鼠的CD 4（+）T细胞在TCR刺激下产生的IFN-γ、IL-4和IL-10水平高于未感染小鼠。这种改变的细胞因子反应依赖于寄生虫血症。为了检查应答的特异性，将来自OT-II TCR转基因小鼠的CD 4（+）T细胞过继转移给小鼠，并用表达OVA的PbA感染小鼠。出乎意料的是，来自OT-II转移的野生型PbA感染小鼠的CD 4（+）T细胞在用OVA刺激后显示出高水平的IFN-γ产生，并且产生IFN-γ的细胞不是OT-II，而是宿主CD 4（+）T细胞。进一步的研究表明，宿主CD 4（+）T细胞产生IFN-γ，以响应活化的OT-II细胞产生的IL-2。这种IFN-γ应答被抗CD 25单克隆抗体完全抑制，并且这种作用不是由于IL-2提供的存活信号的阻断。此外，CD 4（+）T细胞对PbA抗原的应答产生IFN-γ依赖于IL-2。这些发现表明在疟疾寄生虫感染期间IL-2水平的重要性，并表明CD 4（+）T细胞可以通过旁观者机制响应于其他活化的CD 4（+）T细胞产生的IL-2而产生IFN-γ，而无需TCR参与。
T-cell immune responses are critical for protection of the host and for disease pathogenesis during infection with Plasmodium species. We examined the regulation of CD4(+) T-cell cytokine responses during infection with Plasmodium berghei ANKA (PbA). CD4(+) T cells from PbA-infected mice produced IFN-gamma, IL-4 and IL-10 in response to TCR stimulation at levels higher than those from uninfected mice. This altered cytokine response was dependent on parasitemia. To examine the specificity of the response, mice were adoptively transferred with CD4(+) T cells from OT-II TCR transgenic mice and were infected with PbA expressing OVA. Unexpectedly, CD4(+) T cells from the OT-II-transferred wild-type PbA-infected mice showed high levels of IFN-gamma production after stimulation with OVA and the cells producing IFN-gamma were not OT-II but were host CD4(+) T cells. Further investigation revealed that host CD4(+) T cells produced IFN-gamma in response to IL-2 produced by activated OT-II cells. This IFN-gamma response was completely inhibited by anti-CD25 mAbs, and this effect was not due to the block of the survival signals provided by IL-2. Furthermore, IFN-gamma production by CD4(+) T cells in response to PbA antigens was dependent on IL-2. These findings suggest the importance of IL-2 levels during infection with malaria parasites and indicate that CD4(+) T cells can produce IFN-gamma without TCR engagement via a bystander mechanism in response to IL-2 produced by other activated CD4(+) T cells.