IL‐9 is involved in various T cell‐dependent inflammatory models including colitis, encepahlitis, and asthma. However, the regulation and specificity of IL‐9 responsiveness by T cells during immune responses remains poorly understood. Here, we addressed this question using two different models: experimental colitis induced by transfer of naive CD4⁺CD45RB^high T cells into immunodeficient mice, and OVA‐specific T cell activation. In the colitis model, constitutive IL‐9 expression exacerbated inflammation upon transfer of CD4⁺CD45RB^high T cells from WT but not from Il9r ^−/− mice, indicating that IL‐9 acts directly on T cells. Suprisingly, such naïve CD4⁺CD45RB^high T cells failed to express the Il9r or respond to IL‐9 in vitro, in contrast with CD4⁺CD45RB^low T cells. By using OVA‐specific T cells, we observed that T cells acquired the capacity to respond to IL‐9 along with CD44 upregulation, after long‐lasting (5 to 12 days) in vivo antigenic stimulation. Il9r expression was associated with Th2 and Th17 phenotypes. Interestingly, in contrast to the IL‐2 response, antigen restimulation downregulated IL‐9 responsiveness. Taken together, our results demonstrate that IL‐9 does not act on naïve T cells but that IL‐9 responsiveness is acquired by CD4⁺ T cells after in vivo activation and acquisition of memory markers such as CD44.

中文翻译：

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IL-9在经历过抗原的鼠T细胞上发挥生物学功能，并加剧了过继转移诱导的结肠炎。

IL-9参与了各种依赖T细胞的炎症模型，包括结肠炎，脑脊髓炎和哮喘。但是，人们对T细胞在免疫应答过程中对IL-9应答的调节和特异性了解甚少。在这里，我们使用两种不同的模型解决了这个问题：由幼稚的CD4 ⁺ CD45RB^高T细胞转移到免疫缺陷小鼠中引起的实验性结肠炎，以及OVA特异性T细胞活化。在结肠炎模型中，当WT转移CD4 ⁺ CD45RB^高T细胞但不转移Il9r ^-/-小鼠时，组成性IL-9表达加剧炎症，表明IL-9直接作用于T细胞。令人惊讶的是，如此幼稚的CD4 ⁺ CD45RB与CD4 ⁺ CD45RB^低T细胞相比，^高T细胞无法在体外表达Il9r或对IL-9作出反应。通过使用OVA特异性T细胞，我们观察到T细胞在体内抗原刺激（持续5至12天）后获得了对IL-9的反应以及CD44的上调。Il9r表达与Th2和Th17表型有关。有趣的是，与IL-2反应相反，抗原重新刺激下调了IL-9反应性。两者合计，我们的结果表明IL-9不会作用于幼稚T细胞，但在体内激活并获得记忆标记（例如CD44）后，CD4 ⁺ T细胞会获得IL-9应答。