IL-2 and autocrine IL-4 drive the in vivo development of antigen-specific Th2 T cells elicited by nematode parasites
IL-2 and autocrine IL-4 drive the in vivo development of antigen-specific Th2 T cells elicited by nematode parasites
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DOI：
10.4049/jimmunol.174.4.2242
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发表时间：
2005-02-15
影响因子：
4.4
通讯作者：
Gause, WC
中科院分区：
文献类型：
--
作者：
Liu, ZG;Liu, Q;Gause, WC
肠道线虫寄生虫巴西尼波斯特罗线虫会触发强大的2型免疫。以卵清蛋白多肽为模型抗原，研究了该寄生虫对幼稚DO11.10 T细胞体内发育抗原特异性Th2细胞的佐剂作用。我们的发现表明，在受体IL-4(-/-)小鼠中，转移的幼稚OVA特异性DO11.10 T细胞可以发育成Th2细胞。然而，自分泌IL-4是Th2细胞原位分化所必需的，因为在接种IL-4(-/-)受体的小鼠中，转移的IL-4Rα缺陷的DO11.10T细胞显著减少了Th2细胞的发育。令人惊讶的是，我们还发现，IL-2阻断促进了B7依赖的T细胞周期，但抑制了OVA特异性Th2细胞的发育。此外，IL-2的作用不依赖于CD25(+)T调节细胞。这些研究确定了线虫寄生虫引起的Th2反应中需要自分泌IL-4和IL-2，这一点以前并不为人所知。
The intestinal nematode parasite, Nippostrongylus brasiliensis, triggers potent type 2 immunity. Using OVA peptide as a model Ag, we have examined the adjuvant effects of this parasite on the in vivo development of Ag-specific Th2 cells from naive DO11.10 T cells. Our findings show that Th2 cells can develop from transferred naive OVA-specific DO11.10 T cells in recipient IL-4(-/-) mice inoculated with N. brasiliensis plus OVA. However, autocrine IL-4 is required for in situ Th2 cell differentiation since transferred IL-4Ralpha-deficient DO11.10 T cells showed greatly reduced Th2 cell development in inoculated IL-4(-/-) recipient mice. Surprisingly, we also found that IL-2 blockade promoted B7-dependent T cell cycling, but inhibited the development of OVA-specific Th2 cells. Furthermore, the effects of IL-2 occurred independently of CD25(+) T regulatory cells. These studies establish a previously unrecognized requirement for autocrine IL-4 and IL-2 in Th2 responses elicited by nematode parasites.