IL-2 Regulates CD103 Expression on CD4+ T Cells in Scurfy Mice that Display Both CD103-Dependent and Independent Inflammation
IL-2 Regulates CD103 Expression on CD4+ T Cells in Scurfy Mice that Display Both CD103-Dependent and Independent Inflammation
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DOI：
10.4049/jimmunol.0804354
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发表时间：
2009-07-15
影响因子：
4.4
通讯作者：
Ju, Shyr-Te
中科院分区：
文献类型：
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作者：
Sharma, Rahul;Sung, Sun-sang Joe;Ju, Shyr-Te
Scurfy（Sf）小鼠缺乏CD 4（+）Foxp 3（+）调节性T细胞，并发生由CD 4（+）T细胞介导的致命性多器官炎症（MOI）。将IL 2（-/-）基因导入Sf小鼠（Sf. IL 2（-/-）），可抑制皮肤和肺的炎症反应。作为器官的主要整合素受体，我们比较了B6、I12（-/-）、Sf和Sf.I12（-/-）小鼠的CD 4 + T细胞上的CD 103表达。IL 2（-/-）主要特异性抑制Sf小鼠CD 4（+）T细胞中CD 103的表达，而不影响CD 8（+）T细胞和CD 11 c（+）树突状细胞的表达。此外，IL 2（-/-）小鼠中CD 4（+）Foxp 3（+）调节性T细胞CD 103表达未降低。与年龄匹配的Sf小鼠相比，将CD 103（-/-）引入Sf小鼠抑制皮肤和肺中的炎症，但它们在接近7周龄时死亡，皮肤、肺和结肠中出现炎症，证明了由CD 103非依赖性机制诱导的致命MOI。与CD 103（-）CD 4（+）T细胞相比，Sf CD 4（+）T细胞的转移更快地诱导MOI，表明存在CD 103依赖性炎症机制。用抗CD 3加抗CD 28珠进行的体外刺激证实，IL 2（-/-）和Sf. IL 2（-/-）中CD 4（+）Foxp 3（-）T细胞中的CD 103诱导是有缺陷的，并且不能被rIL-2或rIL-15恢复。这些数据表明，IL-2是Sf小鼠中CD 4（+）T细胞上最佳CD 103诱导所必需的，这种作用以器官特异性方式促进炎症。IL-2还具有额外的作用，因为Sf.II2（-/-）小鼠而不是Sf.CD103（-/-）小鼠中的皮肤和肺部炎症的保护是终身的，并且Sf.II2（-/-）小鼠比Sf.CD103（-/-）小鼠具有更长的寿命。免疫学杂志，2009，183：1065-1073.
Scurfy (Sf) mice lack CD4(+)Foxp3(+) regulatory T cells and develop fatal multiorgan inflammation (MOI) mediated by CD4(+) T cells. Introducing Il2(-/-) gene into Sf mice (Sf.Il2(-/-)) inhibited inflammation in skin and lung. As a major integrin receptor for the organs, we compared CD103 expression on the CD4+ T cells of B6, Il2(-/-), Sf, and Sf.Il2(-/-) mice. CD103(+)CD4(+) T cells, but not CD8(+) T cells or CD11c(+) dendritic cells, were significantly up-regulated only in Sf mice, indicating Il2(-/-) dominantly and specifically inhibited CD103 up-regulation in Sf CD4(+) T cells. In addition, CD4(+)Foxp3(+) regulatory T cell CD103 expression was not reduced in Il2(-/-) mice. Introducing CD103(-/-) into Sf mice inhibited inflammation in skin and lung as compared with age-matched Sf mice, but they died at similar to 7 wk old with inflammation developed in skin, lungs, and colon, demonstrating fatal MOI induced by CD103-independent mechanism. Transfer of Sf CD4(+) T cells induced MOI more rapidly than CD103(-)CD4(+) T cells, indicating the presence of CD103-dependent mechanism for inflammation. In vitro stimulation with anti-CD3 plus anti-CD28 beads confirmed that CD103 induction in the CD4(+)Foxp3(-) T cells in Il2(-/-) and Sf.Il2(-/-) is defective and cannot be restored by rIL-2 or rIL-15. The data indicate that IL-2 is required for optimal CD103 induction on CD4(+) T cells in Sf mice and this effect contributes to inflammation in an organ-specific manner. IL-2 also has additional roles because the protection of skin and lung inflammation in Sf.Il2(-/-), but not Sf.CD103(-/-) mice is lifelong and Sf.Il2(-/-) mice have longer lifespan than Sf.CD103(-/-) mice. The Journal of Immunology, 2009, 183: 1065-1073.