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首页> 美国卫生研究院文献>Heliyon >Combination of IL-10 and IL-2 induces oligoclonal human CD4 T cell expansion during xenogeneic and allogeneic GVHD in humanized mice
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Combination of IL-10 and IL-2 induces oligoclonal human CD4 T cell expansion during xenogeneic and allogeneic GVHD in humanized mice

机译：IL-10和IL-2的组合在人源化和异源GVHD诱导人源化小鼠中的寡克隆人CD4 T细胞扩增

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摘要

IL-10 is a crucial anti-inflammatory cytokine which can also exert a seemingly divergent immunostimulatory effects under certain conditions. We found high levels of the cytokine in a xenogeneic GVHD model where NOD-scid IL2rγcnull (NSG) mice were transplanted with human PBMCs in presence of IL-2. Presence of exogenous IL-10 altered the kinetics of IL-2 induced human T cell reconstitution in vivo, showing an initial delay, followed by rapid expansion. Further, compared to IL-2 alone, treatment with IL-2 in combination with IL-10 increased survival in most animals and completely protected ∼20% of mice from GVHD. Additionally, IL-2 induced expansion of both CD4+ and CD8+ xenoreactive T cells whereas a combination of IL-2 and IL-10 resulted in selective expansion of CD4+ T cells only. TCR Vβ repertoire analysis of CD4+ T cells showed that in contrast to IL-2 alone, simultaneous presence of both cytokines drastically reduced the Vβ repertoire of the expanded CD4+ T cells. Highly restricted Vβ usage was also observed when the cytokine combination was tested in an allogeneic GVHD model where NOD-scid IL2rγcnull mice expressing HLA-DR4 (NSG-DR4) were transplanted with purified CD4+ T cells from HLA-DR4 negative donors. Taken together, our results demonstrate that IL-10 can profoundly modulate the subset composition and repertoire of responding T cells during GVHD.
机译：IL-10是至关重要的抗炎细胞因子，在某些条件下也可以发挥看似不同的免疫刺激作用。我们在异种GVHD模型中发现了高水平的细胞因子，在该模型中，在存在IL-2的情况下将NOD-scidIL2rγcnull（NSG）小鼠移植了人P​​BMC。外源性IL-10的存在改变了IL-2诱导的人体内T细胞重构的动力学，显示出最初的延迟，随后迅速扩增。此外，与单独的IL-2相比，用IL-2与IL-10联合治疗可提高大多数动物的存活率，并完全保护约20％的小鼠免受GVHD感染。此外，IL-2诱导CD4 + 和CD8 + 异种反应性T细胞扩增，而IL-2和IL-10的组合导致CD4 + 个T细胞。对CD4 + T细胞的TCRVβ谱分析表明，与单独的IL-2相比，两种细胞因子的同时存在大大降低了扩增的CD4 + T细胞的Vβ谱。 。在同种异体GVHD模型中测试细胞因子组合时，还观察到高度限制的Vβ使用，其中将表达HLA-DR4（NSG-DR4）的NOD-scidIL2rγc null 小鼠移植了纯化的CD4 + 来自HLA-DR4阴性供体的T细胞。两者合计，我们的结果表明IL-10可以深刻调节GVHD期间应答T细胞的亚组组成和组成。

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