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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Allogeneic apoptotic thymocyte-stimulated dendritic cells expand functional regulatory T cells.
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Allogeneic apoptotic thymocyte-stimulated dendritic cells expand functional regulatory T cells.

机译:异体凋亡的胸腺细胞刺激的树突状细胞扩展功能性调节性T细胞。

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摘要

Dendritic cells (DCs) play an important role in the clearance of apoptotic cells. The removal of apoptotic cells leads to peripheral tolerance, although their role is still not clear. We show that the uptake of apoptotic thymocytes by DCs converts these cells into tolerogenic DCs resistant to maturation by lipopolysaccharide, modulating the production of interleukin-12 and up-regulating the expression of transforming growth factor-beta(1) latency associated peptide. We also observed that DCs pulsed with apoptotic cells in the allogeneic context were more efficient in the expansion of regulatory T cells (Tregs), and that this expansion requires contact between DCs and the T cell. The Tregs sorted from in vitro culture suppressed the proliferation of splenocytes in vitro in a specific and non-specific manner. In the in vivo model, the transfer of CD4(+) CD25(-) cells to Nude mice induced autoimmunity, with cell infiltrate found in the stomach, colon, liver and kidneys. The co-transfer of CD4(+) CD25(-) and CD4(+) CD25(+) prevented the presence of cell infiltrates in several organs and increased the total cell count in lymph nodes. Our data indicate that apoptotic cells have an important role in peripheral tolerance via induction of tolerogenic DCs and CD4(+) CD25(+) Foxp3(+) cells that present regulatory functions.
机译:树突状细胞(DCs)在清除凋亡细胞中起重要作用。凋亡细胞的去除导致外周耐受,尽管它们的作用尚不清楚。我们表明,DC摄取凋亡的胸腺细胞会将这些细胞转化为耐受脂多糖成熟的DC,调节白介素12的产生并上调转化生长因子-β(1)潜伏期相关肽的表达。我们还观察到,在同种异体情况下,用凋亡细胞脉冲产生的DC在调节性T细胞(Tregs)的扩增中更为有效,并且这种扩展需要DC与T细胞之间的接触。从体外培养物中分选的Tregs以特异性和非特异性方式抑制了脾细胞的体外增殖。在体内模型中,CD4(+)CD25(-)细胞向裸鼠的转移诱导自身免疫,并在胃,结肠,肝和肾中发现细胞浸润。 CD4(+)CD25(-)和CD4(+)CD25(+)的共同转移阻止了几个器官中细胞浸润的存在,并增加了淋巴结中的总细胞数。我们的数据表明,凋亡细胞通过诱导致耐受性DC和呈现调节功能的CD4(+)CD25(+)Foxp3(+)细胞在外周耐受中具有重要作用。

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