Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Eur J Immunol. 2010 May;40(5):1396-407. doi: 10.1002/eji.200940093.
Signaling via the IL-7 receptor complex (IL-7Ralpha/CD127 and IL-2Rgamma/CD132) is required for T-cell development and survival. Decreased CD127 expression has been associated with persistent viral infections (e.g. HIV, HCV) and cancer. Many IL-2Rgamma-sharing (gammaC) cytokines decrease CD127 expression on CD4+ and CD8+ T cells in mice (IL-2, IL-4, IL-7, IL-15) and in humans (IL-2, IL-7), suggesting a common function. IL-4 is of particular interest as it is upregulated in HIV infection and in thyroid and colon cancers. The role of IL-4 in regulating CD127 expression and IL-7 activity in human thymocytes and mature CD8+ T cells is unknown and was therefore investigated. IL-4 decreased CD127 expression on all thymocyte subsets tested and only on naïve (CD45RA+) CD8+ T cells, without altering membrane-bound CD127 mRNA expression. Pre-treatment of thymocytes or CD8+ T cells with IL-4 inhibited IL-7-mediated phosphorylation of STAT5 and decreased proliferation of CD8+ T cells. By downregulating CD127 expression and signaling on developing thymocytes and CD8+ T cells, IL-4 is a potential contributor to impaired CD8+ T-cell function in some anti-viral and anti-tumor responses. These findings are of particular consequence to diseases such as HIV, HCV, RSV, measles and cancer, in which CD127 expression is decreased, IL-7 activity is impaired and IL-4 concentrations are elevated.
通过 IL-7 受体复合物（IL-7Ralpha/CD127 和 IL-2Rgamma/CD132）的信号传导对于 T 细胞的发育和存活是必需的。CD127 表达的降低与持续性病毒感染（例如 HIV、HCV）和癌症有关。许多共享 IL-2Rgamma（gammaC）细胞因子在小鼠（IL-2、IL-4、IL-7、IL-15）和人类（IL-2、IL-7）的 CD4+和 CD8+T 细胞上降低 CD127 的表达，表明存在共同的功能。IL-4 特别有趣，因为它在 HIV 感染和甲状腺癌和结肠癌中上调。IL-4 在调节人胸腺细胞和成熟 CD8+T 细胞中 CD127 表达和 IL-7 活性中的作用尚不清楚，因此进行了研究。IL-4 降低了所有测试的胸腺细胞亚群上的 CD127 表达，而仅在幼稚（CD45RA+）CD8+T 细胞上降低，而不改变膜结合的 CD127 mRNA 表达。IL-4 预处理胸腺细胞或 CD8+T 细胞可抑制 IL-7 介导的 STAT5 磷酸化，并降低 CD8+T 细胞的增殖。通过下调发育中的胸腺细胞和 CD8+T 细胞上的 CD127 表达和信号传导，IL-4 可能是某些抗病毒和抗肿瘤反应中 CD8+T 细胞功能受损的潜在因素。这些发现对于 HIV、HCV、RSV、麻疹和癌症等疾病具有特别重要的意义，在这些疾病中，CD127 表达降低，IL-7 活性受损，IL-4 浓度升高。
