IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor α subunit CD25
IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor α subunit CD25
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DOI：
10.1073/pnas.0909384107
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发表时间：
2010-02-02
影响因子：
11.1
通讯作者：
Boyman, Onur
中科院分区：
文献类型：
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作者：
Letourneau, Sven;van Leeuwen, Ester M. M.;Boyman, Onur
IL-2对T细胞，尤其是CD4(+)T调节细胞和记忆性CD8(+)细胞的动态平衡至关重要，注射超激动剂IL-2/抗IL-2抗体复合物后，这些细胞在体内的旺盛增殖就证明了这一点。由于缺乏对IL-2动态平衡的了解，IL-2/抗IL-2抗体复合物的作用机制尚不清楚。我们发现IL-2受体α(CD25)在IL-2动态平衡中起着关键作用。因此，延长IL-2半衰期和使用抗体或CD25缺陷小鼠阻断CD25会导致IL-2介导的T细胞增殖，类似于IL-2/抗IL-2抗体复合体，但不是单独使用。这些数据表明，CD25在IL-2动态平衡中的作用是不可预测的。
IL-2 is crucial to T cell homeostasis, especially of CD4(+) T regulatory cells and memory CD8(+) cells, as evidenced by vigorous proliferation of these cells in vivo following injections of superagonist IL-2/anti-IL-2 antibody complexes. The mechanism of IL-2/anti-IL-2 antibody complexes is unknown owing to a lack of understanding of IL-2 homeostasis. We show that IL-2 receptor alpha (CD25) plays a crucial role in IL-2 homeostasis. Thus, prolongation of IL-2 half-life and blocking of CD25 using antibodies or CD25-deficient mice led in combination, but not alone, to vigorous IL-2-mediated T cell proliferation, similar to IL-2/anti-IL-2 antibody complexes. These data suggest an unpredicted role for CD25 in IL-2 homeostasis.