Plum J, De Smedt M, Leclercq G, Vandekerckhove B
Department of Clinical Chemistry, Microbiology and Immunology, University of Ghent, University Hospital, Belgium.
J Immunol. 1995 Jun 1;154(11):5789-98.
TGF-beta is a multifunctional growth regulator that can either inhibit or stimulate the growth and differentiation of lymphocytes. For several cell types the effect of TGF-beta was found to correlate with the differentiation stage of the cells. We have studied the influence of TGF-beta on the differentiation of murine thymocytes by evaluating the effect of TGF-beta on the generation of thymocyte subpopulations in fetal thymus organ culture. TGF-beta inhibited the growth and differentiation of CD4-CD8- double-negative thymocytes. In the CD4-CD8- double-negative cell population, most cells remained CD44+CD25-, with CD44+CD25+ and CD44-CD25- subpopulations dramatically decreased in cell numbers. The accumulation of cells with a phenotype characteristic of cells in early stage of differentiation suggests a block at very early transition steps. These observations were confirmed in experiments with precursor cells from fetal liver transferred to 2-deoxyguanosine-treated alymphoid thymic lobes, inasmuch as addition of TGF-beta caused a complete inhibition of T cell development. Differentiation into CD4+CD8+ double-positive thymocytes and CD4+ single-positive thymocytes was impaired because these cell numbers were greatly reduced. In contrast, the CD8+ single-positive subpopulation retained normal cell numbers. This CD8+ population had characteristics of a mature subset as the cells expressed CD8 beta and high levels of TCR-alpha beta and CD3. This TCR-alpha beta + cell population was not actively dividing, suggesting that these cells arise de novo by differentiation.
转化生长因子-β（TGF-β）是一种多功能生长调节因子，它既可以抑制也可以刺激淋巴细胞的生长和分化。对于几种细胞类型，已发现TGF-β的作用与细胞的分化阶段相关。我们通过评估TGF-β对胎胸腺器官培养中胸腺细胞亚群生成的影响，研究了TGF-β对小鼠胸腺细胞分化的影响。TGF-β抑制CD4-CD8-双阴性胸腺细胞的生长和分化。在CD4-CD8-双阴性细胞群体中，大多数细胞仍为CD44+CD25-，而CD44+CD25+和CD44-CD25-亚群的细胞数量显著减少。具有早期分化细胞表型特征的细胞积累表明在非常早期的过渡步骤存在阻滞。这些观察结果在将胎肝前体细胞转移至经2-脱氧鸟苷处理的无淋巴细胞胸腺叶的实验中得到证实，因为添加TGF-β会导致T细胞发育完全受到抑制。向CD4+CD8+双阳性胸腺细胞和CD4+单阳性胸腺细胞的分化受损，因为这些细胞数量大幅减少。相比之下，CD8+单阳性亚群的细胞数量保持正常。这个CD8+群体具有成熟亚群的特征，因为细胞表达CD8β以及高水平的TCR-αβ和CD3。这个TCR-αβ+细胞群体没有活跃分裂，表明这些细胞是通过分化重新产生的。
