Zhang Y, Chen P, Zhang Y
Immunology Research Unit, Suzhou Medical College, P.R. China.
Zhonghua Yi Xue Za Zhi. 1999 Mar;79(3):178-80.
To investigate the regulatory effect of transforming growth factor-beta 1 (TGF-beta 1) on the generation of dendritic cells (DCs) from hematopoietic progenitor cells (HPCs) and its cellular and molecular mechanisms.
Murine bone marrow derived-Lin c-kit+ HPCs were isolated by a cell sorter and cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), tumor necrosis factor alpha(TNF alpha) and TGF-beta 1. The generation of DC precursors and mature DCs and their phenotypes were analyzed by a cell sorter, reverse transcription-polymerase chain reaction (RT-PCR), and allogenic mixed lymphocyte reaction (MLR).
TGF-beta 1 could significantly inhibit the generation of DC precursors at day 6 and mature DCs at day 12 from murine Lin- c-kit+ HPCs stimulated with GM-CSF + SCF + TNF alpha or GM-CSF + SCF. Moreover, TGF-beta 1 markedly suppressed the expression of antigen peresenting molecule Ia and co-stimulatory molecule CD86 on the surface of cultured Lin- c-kit+ HPCs. Examination of RT-PCR showed that TGF-beta 1 could also inhibit the expression of MHC class II trans-activator (CTIIA) mRNA, which encodes a transcriptional factor to strictly control the expression of MHC class II antigens in the cultured cells.
Our results suggest that TGF-beta 1 is an inhibitory cytokine for the generation of DC precursors and maturation of DC from HPCs, which may account for the cellular mechanisms of TGF-beta 1-mediated immuno-suppressive functions in vivo and in vitro.
研究转化生长因子β1（TGF-β1）对造血祖细胞（HPCs）来源的树突状细胞（DCs）生成的调节作用及其细胞和分子机制。
通过细胞分选仪分离小鼠骨髓来源的Lin⁻c-kit⁺ HPCs，并在粒细胞-巨噬细胞集落刺激因子（GM-CSF）、干细胞因子（SCF）、肿瘤坏死因子α（TNFα）和TGF-β1存在的条件下进行培养。通过细胞分选仪、逆转录-聚合酶链反应（RT-PCR）和同种异体混合淋巴细胞反应（MLR）分析DC前体细胞和成熟DCs的生成及其表型。
TGF-β1可显著抑制GM-CSF + SCF + TNFα或GM-CSF + SCF刺激的小鼠Lin⁻c-kit⁺ HPCs在第6天DC前体细胞和第12天成熟DCs的生成。此外，TGF-β1显著抑制培养的Lin⁻c-kit⁺ HPCs表面抗原呈递分子Ia和共刺激分子CD86的表达。RT-PCR检测显示，TGF-β1还可抑制MHC II类反式激活因子（CIITA）mRNA的表达，CIITA是一种转录因子，可严格控制培养细胞中MHC II类抗原的表达。
我们的结果表明，TGF-β1是HPCs来源的DC前体细胞生成及DC成熟的抑制性细胞因子，这可能解释了TGF-β1在体内和体外介导免疫抑制功能的细胞机制。
