Division of Immunology and Allergy, University Hospital of Lausanne, CH-1011 Lausanne, Switzerland.
Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2171-6. doi: 10.1073/pnas.0909384107. Epub 2010 Jan 19.
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.
IL-2 对于 T 细胞的稳态至关重要,尤其是对于 CD4(+)T 调节细胞和记忆性 CD8(+)细胞,这一点可以从体内注射超强激动剂 IL-2/抗 IL-2 抗体复合物后这些细胞的强烈增殖中得到证明。由于缺乏对 IL-2 稳态的理解,IL-2/抗 IL-2 抗体复合物的机制尚不清楚。我们表明,IL-2 受体 alpha(CD25)在 IL-2 稳态中起着关键作用。因此,使用抗体或缺乏 CD25 的小鼠延长 IL-2 的半衰期并阻断 CD25,两者联合使用,但不是单独使用,会导致类似于 IL-2/抗 IL-2 抗体复合物的强烈的 IL-2 介导的 T 细胞增殖。这些数据表明 CD25 在 IL-2 稳态中具有意想不到的作用。