BACKGROUND CD8+CD28- T suppressor (Ts) cells play critical role in transplant tolerance. Our previous study has generated CD8+CD28- Ts cells in vitro which exert robust allospecific suppressive capacity in vitro. RESULTS CD8+CD28- Ts cells were expanded by stimulating human CD8+ T cells with allogeneic antigen presenting cells in the presence of the common gamma chain cytokines IL-2, IL-7 and IL-15 in vitro, and were further verified in vitro through day 7 to 11 for their persistency of the allospecific suppressive capacity. When CD8+CD28- Ts cells were adoptively transferred into NOG mice, their capacity to inhibit CD4+ T cell proliferation in allospecific manner remained potent on 11 days after their injection. The mechanisms for expansion of CD8+CD28- Ts cells by the common gamma chain cytokines were investigated. These included promoting CD8+CD28- T cells proliferation, converting CD8+CD28+ T cells to CD8+CD28- T cells and decreasing CD8+CD28- T cell death. Furthermore, the expanded CD8+CD28- Ts cells showed upregulation of the co-inhibitory molecule Tim-3 and down-regulation of the cytotoxic molecule granzyme B. CONCLUSIONS In summary, these results demonstrated that the in vitro-expanded human CD8+CD28- T cells retained potent allospecific suppressive capacity in vivo and depicted multiple mechanisms for the expansion of Ts cells, which might promote further bench to clinic research.

中文翻译：

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通过常见γ链（γc）细胞因子扩增的人CD8 + CD28-T抑制细胞在体内保持稳定的同种异体抑制能力。

背景技术CD8 + CD28-T抑制子（Ts）细胞在移植耐受中起关键作用。我们先前的研究已经在体外产生了CD8 + CD28-Ts细胞，这些细胞在体外具有强大的同种异体抑制能力。结果在存在共同的γ链细胞因子IL-2，IL-7和IL-15的条件下，通过用同种异体抗原呈递细胞刺激人CD8 + T细胞来扩增CD8 + CD28-Ts细胞，并通过体外进一步验证第7天到第11天是他们对同种异体抑制能力的持久性。当CD8 + CD28-Ts细胞过继转移到NOG小鼠中时，它们以同种特异性方式抑制CD4 + T细胞增殖的能力在注射后11天仍然有效。研究了常见的γ链细胞因子扩增CD8 + CD28-Ts细胞的机制。这些包括促进CD8 + CD28-T细胞增殖，将CD8 + CD28 + T细胞转化为CD8 + CD28-T细胞和减少CD8 + CD28-T细胞死亡。此外，扩增的CD8 + CD28-Ts细胞表现出共抑制分子Tim-3的上调和细胞毒性分子颗粒酶B的下调。结论总之，这些结果表明，体外扩增的人CD8 + CD28-Ts细胞具有上调的抑制作用。 T细胞在体内保留了强大的同种异体抑制能力，并描绘了多种扩展Ts细胞的机制，这可能会促进临床研究的进一步发展。