摘要
目的研究转化生长因子β１（ＴＧＦβ１）对造血祖细胞（ＨＰＣ）产生树突状细胞（ＤＣ）的调控作用及其分子机理。方法分离高纯度小鼠骨髓Ｌｉｎ、Ｃｋｉｔ＋、ＨＰＣ，经粒细胞集落刺激因子（ＧＭＣＳＦ）、干细胞因子（ＳＣＦ）和肿瘤坏死因子（ＴＮＦα）培养，诱导产生ＤＣ。采用流式细胞仪、逆转录多聚酶链反应（ＲＴＰＣＲ）和同种异基因混合淋巴细胞反应（ＡｌｏＭＬＲ），分析ＴＧＦβ１对ＤＣ产生的调节作用及其分子机理。结果ＴＧＦβ１显著抑制ＤＣ前体细胞的产生和成熟ＤＣ的分化，同时ＴＧＦβ１抑制主组织相容性抗原（ＭＨＣⅡ）类抗原活化转录因子（ＣＩＴＡ）基因的转录和ＭＨＣⅡ类抗原与协同刺激分子ＣＤ８６抗原的表达。结论ＴＧＦβ１介导的免疫抑制作用与其抑制ＤＣ的分化及功能成熟相关。
Objective To investigate the regulatory effect of transforming growth factor β1 (TGF β1) on the generation of dendritic cells (DCs) from hematopoietic progenitor cells (HPCs) and its cellular and molecular mechnisms.Methods 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 α(TNFα) and TGF β1. 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).Results TGF β1 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 + TNFα or GM CSF + SCF. Moreover, TGF β1 markedly suppressed the expression of antigen peresenting molecule Ia and co stimulatory molecule CD86 on the surface of cultrued Lin c kit + HPCs. Examination of RT PCR showed that TGF β1 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. Conclusion Our results suggest that TGF β1 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 β1 mediated immuno suppressive functions in vivo and in vitro.
出处
《中华医学杂志》
CAS
CSCD
北大核心
1999年第3期178-180,共3页
National Medical Journal of China
