CD25+CD4+ cells contribute to Th2 polarization during helminth infection by suppressing Th1 response development
CD25+CD4+ cells contribute to Th2 polarization during helminth infection by suppressing Th1 response development
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DOI：
10.4049/jimmunol.173.2.1224
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发表时间：
2004-07-15
影响因子：
4.4
通讯作者：
Pearce, EJ
中科院分区：
文献类型：
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作者：
McKee, AS;Pearce, EJ
感染曼氏血吸虫的小鼠产生极化Th2反应，其中Th1反应被il -10介导的IL-12产生的抑制所阻止。我们发现，受感染小鼠的树突状细胞在响应CD40连接时被诱导产生IL-12，而IL-10通过抑制这一过程起作用。在受感染的小鼠中，CD4（+）细胞的两个亚群（可通过CD25的表达分离）产生IL-10。CD25(+)CD4（+）细胞表达叉头盒P3，抑制CD4(+) T细胞增殖，产生IL-10，但IL-5较少。相比之下，CD25(-)CD4（+）细胞不能表达叉头盒P3或抑制增殖，并占未分离脾细胞群产生的所有IL-5、IL-6和IL-13。因此，CD25（+）和CD25（-）亚群可以分别被表征为调节性T细胞（Treg细胞）和Th2细胞。受感染小鼠的CD25（+）和CD25(-)CD4(+) T细胞在受卵细胞Ag刺激时，能够抑制CD40激动剂刺激的树突状细胞产生IL-12，这与它们制造IL-10的能力一致。此外，在过继性转移实验中，两个CD4（+）细胞亚群都能够部分抑制卵细胞免疫IL-10（-/-）小鼠Th1反应的发展。感染小鼠体内的Treg细胞与天然Treg细胞之间的关系被强烈地证明是通过将来自幼稚小鼠的CD25(+)CD4（+）细胞转移到卵细胞免疫或感染IL-10（-/-）小鼠体内抑制Th1应答发展的能力。这些数据表明，在血吸虫病期间，天然Treg细胞和较小程度上的Th2细胞在抑制Th1反应和确保Th2极化中发挥作用。
Mice infected with Schistosoma mansoni develop polarized Th2 responses in which Th1 responses are prevented by IL-10-mediated suppression of IL-12 production. We show that dendritic cells from infected mice are primed to make IL-12 in response to CD40 ligation, and that IL-10 acts by inhibiting this process. In infected mice, two subpopulations of CD4(+) cells, separable by their expression of CD25, make IL-10. CD25(+)CD4(+) cells expressed forkhead box P3, inhibited proliferation of CD4(+) T cells, and made IL-10, but little IL-5. In contrast, CD25(-)CD4(+) cells failed to express forkhead box P3 or to inhibit proliferation and accounted for all the IL-5, IL-6, and IL-13 produced by unseparated splenic populations. Thus, CD25(+) and CD25(-) subpopulations could be characterized as regulatory T cells (Treg cells) and Th2 cells, respectively. Consistent with their ability to make IL-10, both CD25(+) and CD25(-)CD4(+) T cells from infected mice were able, when stimulated with egg Ag, to suppress IL-12 production by CD40 agonist-stimulated dendritic cells. Additionally, in adoptive transfer experiments, both CD4(+) subpopulations of cells were able to partially inhibit the development of Th1 responses in egg-immunized IL-10(-/-) mice. The relationship of Treg cells in infected mice to natural Treg cells was strongly suggested by the ability of CD25(+)CD4(+) cells from naive mice to inhibit Th1 response development when transferred into egg-immunized or infected IL-10(-/-) mice. The data suggest that natural Treg cells and, to a lesser extent, Th2 cells play roles in suppressing Th1 responses and ensuring Th2 polarization during schistosomiasis.