TGF-beta 1 promotes in vitro generation of dendritic cells by protecting progenitor cells from apoptosis.
TGF-beta 1 promotes in vitro generation of dendritic cells by protecting progenitor cells from apoptosis.
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TGF-β1 通过保护祖细胞免于凋亡来促进树突状细胞的体外生成。
作者：
E. Riedl;H. Strobl;O. Majdic;W. Knapp
我们以前的研究表明，在无血清条件下，从CD34+祖细胞体外高效地产生树突状细胞(DC)需要转化生长因子-β1。在这里，我们表明，转化生长因子-β1促进DC的生长和分化，主要是通过保护DC前体的活性，而不是通过增强其增殖反应。将转化生长因子-β1添加到肿瘤坏死因子-α、粒细胞-巨噬细胞集落刺激因子和干细胞因子添加的培养物中，对周期细胞的比例没有显著影响。然而，在培养72 h时，在有转化生长因子-β1存在的情况下，凋亡细胞的比例下降了60%以上。这种早期的保护作用与培养7天时CD1a+DC数量和比例较高有关。这也与转化生长因子-β1培养细胞Fas/APO-1表达显著降低有关。相反，同样在这些培养条件下产生的粒单核细胞不会受到如此程度的影响。在有无转化生长因子-β1存在的情况下，两者的比例相等。只有在同时存在转化生长因子-β1和肿瘤坏死因子-α的情况下，才能观察到转化生长因子-β1对DC生长的显著促进作用。在缺乏肿瘤坏死因子-α的情况下，转化生长因子-β1抑制而不是促进细胞的扩张。因此，为了在体外发生最佳的DC发育，所有四种细胞因子显然必须协同作用，而转化生长因子-β1和肿瘤坏死因子-α的结合似乎尤其关键。
Our previous studies demonstrated that TGF-beta 1 is required for efficient in vitro generation of dendritic cells (DC) from CD34+ progenitor cells under serum-free conditions. Here we show that TGF-beta 1 promotes the growth and differentiation of DC primarily by protecting the viability of DC precursors and not by enhancing their proliferative response. Addition of TGF-beta 1 to TNF-alpha, granulocyte-macrophage CSF, and stem cell factor-supplemented cultures had no significant effect on the proportions of cycling cells. Already at 72 h of culture, however, the proportion of apoptotic cells was reduced by more than 60% in the presence of TGF-beta 1. This early protective effect of TGF-beta 1 correlates with the outgrowth of higher numbers and proportions of CD1a+ DC at day 7 of culture. It also correlates with a significantly reduced Fas/APO-1 expression on TGF-beta 1 cultured cells. In contrast, granulomonocytic cells, also arising under these culture conditions, are not affected to such an extent. They are found at equal proportions, both in the presence and absence of TGF-beta 1. The striking DC growth-promoting effect of TGF-beta 1 could only be observed when both TGF-beta 1 and TNF-alpha were present in the cultures. TGF-beta 1, in the absence of TNF-alpha, rather inhibited than enhanced cell expansion. Thus, for optimal in vitro DC development to occur, all four cytokines must obviously act in concert and the combination of TGF-beta 1 with TNF-alpha seems to be particularly critical.