Sanarico Nunzia, Ciaramella Antonio, Sacchi Alessandra, Bernasconi Daniela, Bossù Paola, Mariani Francesca, Colizzi Vittorio, Vendetti Silvia
Department of Biology, University of Rome Tor Vergata, Italy.
J Leukoc Biol. 2006 Sep;80(3):555-62. doi: 10.1189/jlb.1105690. Epub 2006 Jun 29.
Interleukin (IL)-2 plays an important role in the control of the immune responses, and it is released in a variety of tissues in response to inflammatory stimuli. As monocytes and mature dendritic cells (DCs) express CD25, the high-affinity subunit of IL-2 receptor, we examined the effect of exogenous IL-2 on the in vitro generation and maturation of DCs from monocytes. Human monocyte-derived DCs (MDDCs) were generated by culturing monocytes with granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-4 in the presence or absence of IL-2. The cytokine was added at the beginning and after 5 days of culture. Our findings indicate that IL-2 does induce monocytes to differentiate into DCs with the same morphology and phenotype of that obtained in the presence of GM-CSF and IL-4 alone, but with some distinctive functional properties. DCs differentiated in the presence of IL-2 secreted significantly more IL-1beta, TNF-alpha, and IL-12 p70 in response to lipopolysaccharide stimulation and induced allogeneic, naïve T cells to release a significantly higher amount of interferon-gamma if compared with DCs obtained by culturing monocytes with GM-CSF and IL-4. These results indicate unrecognized effects of IL-2 on human MDDCs and suggest that an IL-2-rich environment during differentiation and maturation of DCs can modify their T helper cell-inducing properties.
白细胞介素(IL)-2在免疫反应的调控中发挥着重要作用,并且在受到炎症刺激时会在多种组织中释放。由于单核细胞和成熟树突状细胞(DC)表达IL-2受体的高亲和力亚基CD25,我们研究了外源性IL-2对单核细胞来源的DC体外生成和成熟的影响。人单核细胞来源的DC(MDDC)通过在有或无IL-2的情况下,将单核细胞与粒细胞巨噬细胞集落刺激因子(GM-CSF)和IL-4共同培养来生成。细胞因子在培养开始时和培养5天后添加。我们的研究结果表明,IL-2确实能诱导单核细胞分化为DC,其形态和表型与仅在GM-CSF和IL-4存在时获得的DC相同,但具有一些独特的功能特性。与通过将单核细胞与GM-CSF和IL-4共同培养获得的DC相比,在IL-2存在下分化的DC在受到脂多糖刺激时分泌的IL-1β、TNF-α和IL-12 p70显著更多,并且能诱导同种异体幼稚T细胞释放显著更高量的干扰素-γ。这些结果表明IL-2对人MDDC有未被认识到的作用,并提示在DC分化和成熟过程中富含IL-2的环境可改变其诱导辅助性T细胞的特性。