Cutting Edge: OX40 agonists can drive regulatory T cell expansion if the cytokine milieu is right.
Cutting Edge: OX40 agonists can drive regulatory T cell expansion if the cytokine milieu is right.
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DOI：
10.4049/jimmunol.0901112
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发表时间：
2009-10-15
期刊：
影响因子：
--
通讯作者：
Weinberg AD
中科院分区：
文献类型：
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作者：
Ruby CE;Yates MA;Hirschhorn-Cymerman D;Chlebeck P;Wolchok JD;Houghton AN;Offner H;Weinberg AD
我们报告说，OX 40刺激驱动所有谱系的CD 4 T细胞的发展，包括调节性T细胞和可塑性的反应是依赖于当地的细胞因子。在TGF-β1处理的培养物中，OX 40激动剂增加IFN-γ和IL-4的产生，并将T细胞从Treg谱系转向。然而，在0X 40刺激的情况下的细胞因子阻断促进也增强了Treg积累。该观察结果在幼稚小鼠中是明显的，因为0X 40接合增强了体内Treg增殖和积累。最后，0X 40激动剂施用在相反方向上影响EAE疾病的严重程度，这取决于施用的时机。在Ag引发期间给予，0X 40激动剂驱动Treg扩增并抑制疾病，然而，给予之后，其增强CNS中的T细胞效应细胞因子产生并加重疾病。因此，OX 40信号传导可以增加所有CD 4 T细胞谱系的积累;然而，其免疫应答的加重可能具有非常不同的生物学结果，这取决于局部细胞因子环境。
We report that OX40 stimulation drives all lineages of CD4 T cell development including Treg and the plasticity of the response is dependant on local cytokines. In TGF-β1-treated cultures, OX40 agonist increased IFN-γ and IL-4 production and diverted T cells from the Treg lineage. However, cytokine blockade in the context of OX40 stimulation promoted also enhanced Treg accumulation. This observation was evident in naive mice, as OX40 engagement enhanced Treg proliferation and accumulation in vivo. Lastly, OX40 agonist administration influenced EAE disease severity in opposing directions depending on the timing of administration. Given during Ag priming, OX40 agonist drove Treg expansion and inhibited disease, whereas, given later it enhanced T cell effector cytokine production in the CNS and exacerbated disease. Hence, OX40 signaling can augment the accumulation of all CD4 T cell lineages; however its accentuation of immune responses may have vastly different biologic outcomes depending upon the local cytokine milieu.