Boyman Onur, Kovar Marek, Rubinstein Mark P, Surh Charles D, Sprent Jonathan
Department of Immunology, IMM4, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Science. 2006 Mar 31;311(5769):1924-7. doi: 10.1126/science.1122927. Epub 2006 Feb 16.
Interleukin-2 (IL-2), which is a growth factor for T lymphocytes, can also sometimes be inhibitory. Thus, the proliferation of CD8+ T cells in vivo is increased after the injection of a monoclonal antibody that is specific for IL-2 (IL-2 mAb), perhaps reflecting the removal of IL-2-dependent CD4+ T regulatory cells (T regs). Instead, we show here that IL-2 mAb augments the proliferation of CD8+ cells in mice simply by increasing the biological activity of preexisting IL-2 through the formation of immune complexes. When coupled with recombinant IL-2, some IL-2/IL-2 mAb complexes cause massive (>100-fold) expansion of CD8+ cells in vivo, whereas others selectively stimulate CD4+ T regs. Thus, different cytokine-antibody complexes can be used to selectively boost or inhibit the immune response.
白细胞介素-2(IL-2)是T淋巴细胞的生长因子,但有时也具有抑制作用。因此,注射针对IL-2的单克隆抗体(IL-2 mAb)后,体内CD8 + T细胞的增殖会增加,这可能反映了依赖IL-2的CD4 + T调节细胞(Tregs)的清除。相反,我们在此表明,IL-2 mAb通过形成免疫复合物来提高已有IL-2的生物活性,从而增强小鼠体内CD8 +细胞的增殖。当与重组IL-2偶联时,一些IL-2 / IL-2 mAb复合物会导致体内CD8 +细胞大量(> 100倍)扩增,而其他复合物则选择性地刺激CD4 + Tregs。因此,不同的细胞因子-抗体复合物可用于选择性地增强或抑制免疫反应。