IL-2/anti-IL-2 antibody complex enhances vaccine-mediated antigen-specific CD8+ T cell responses and increases the ratio of effector/memory CD8+ T cells to regulatory T cells

IL-2/anti-IL-2 antibody complex enhances vaccine-mediated antigen-specific CD8+ T cell responses and increases the ratio of effector/memory CD8+ T cells to regulatory T cells
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DOI:
10.4049/jimmunol.180.7.5118
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发表时间:
2008-04-01
影响因子:
4.4
通讯作者:
Sabzevari, Helen
Sabzevari, Helen
中科院分区:
医学2区
文献类型:
--
作者:
Mostboeck, Sven;Lutsiak, M. E. Christine;Sabzevari, Helen

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IL-2被很好地描述为具有两种明显不同功能的细胞因子:作为CD 4(+)和CD 8(+)T细胞活化/扩增期间的必需信号,以及作为稳态期间维持CD 4(+)CD 25(+)FoxP 3(+)T细胞(调节性T(T-REG)细胞)的必需细胞因子。在这项研究中,我们首次证明,与单独使用IL-2相比,IL-2和抗IL-2 Ab的复合物(IL-2复合物)在具有已知抗原特异性的小鼠模型中增强了病毒疫苗的有效性。IL-2复合物导致在疫苗接种环境中Ag特异性再刺激后Ag特异性效应/记忆CD 8(+)T细胞、细胞因子产生和CTL裂解的数量增加。我们的研究结果进一步表明,这种作用是暂时的,并在IL-2复合物治疗周期后的几天内下降。此外,与单独使用IL-2相比,IL-2复合物大大增加了效应/记忆CD 8(+)T细胞与T-REG细胞的比例。因此,这种现象可以潜在地用于增强对疫苗接种的免疫应答。
IL-2 is well described as a cytokine with two markedly distinct functionalities: as a necessary signal during CD4(+) and CD8(+) T cell activation/expansion and as an essential cytokine for the maintenance of CD4(+)CD25(+)FoxP3(+) T cells (regulatory T (T-REG) cells) during homeostasis. In this study we demonstrate for the first time that, compared with the use of IL-2 alone, a complex of IL-2 and anti-IL-2 Ab (IL-2 complex) enhances the effectiveness of a viral vaccine in a mouse model with known Ag specificity. IL-2 complex led to an increase in the number of Ag-specific effector/memory CD8(+) T cells, cytokine production, and CTL lysis following Ag-specific restimulation in a vaccination setting. Our results further demonstrate that this effect is temporary and declines over the course of a few days after the IL-2 complex treatment cycle. Moreover, in contrast to the use of IL-2 alone, IL-2 complex greatly increased the ratio of effector/memory CD8(+) T cells to T-REG cells. This phenomenon can thus potentially be used in the enhancement of immune responses to vaccination.