TGF-β type II receptor-deficient thymocytes develop normally but demonstrate increased CD8+ proliferation in vivo
TGF-β type II receptor-deficient thymocytes develop normally but demonstrate increased CD8+ proliferation in vivo
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DOI：
10.1182/blood-2005-05-1871
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发表时间：
2005-12-15
期刊：
影响因子：
20.3
通讯作者：
Karlsson, S
中科院分区：
文献类型：
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作者：
Levéen, P;Carlsén, M;Karlsson, S
我们利用Cre/lox系统构建了一个转化生长因子β受体II（TβRII）诱导性缺陷的小鼠模型。通过这种方法，转化生长因子β（TGF -β）信号传导缺陷可通过骨髓移植局限于造血系统。接受TβRII -/-骨髓移植的小鼠会发生一种致命的炎症性疾病，与TGF -β1基因缺失小鼠的情况非常相似。先前的体外研究表明，TGF -β在T细胞发育中具有多种作用，包括增殖、凋亡和分化。我们利用我们的移植模型来探究在缺乏TGF -β信号传导的情况下T细胞发育是否正常。研究结果首次在体内和胎儿胸腺器官培养（FTOC）中表明，就CD4、CD8、CD25和CD44的表达模式所定义的胸腺T细胞发育的整个途径而言，胸腺细胞分化并不需要TGF -β。与先前的研究相反，未观察到胸腺细胞凋亡增加。然而，通过体内溴脱氧尿苷（BrdU）掺入测定，TβRII缺陷型CD8(+)胸腺细胞的增殖率增加了2倍。这些结果强调了TGF -β作为对T细胞功能至关重要的免疫调节剂的重要性。
We have taken advantage of the Cre/lox system to generate a mouse model with inducible deficiency of transforming growth factor beta receptor II (T beta RII). Using this approach, transforming growth factor beta (TGF-beta) signaling deficiency can be restricted to the hematopoietic system by bone marrow transplantation. Mice that received transplants with T beta RII-/- bone marrow develop a lethal inflammatory disorder closely resembling that of TGF-beta 1-null mice. Previous in vitro studies have suggested multiple roles for TGF-beta in T-cell development, including proliferation, apoptosis, and differentiation. We used our transplantation model to ask whether T-cell development is normal in the absence of TGF-beta signalling. The findings show for the first time in vivo and in fetal thymus organ culture (FTOC) that TGF-beta is not required for thymocytes to differentiate along the entire pathway of thymic T-cell development, as defined by the expression patterns of CD4, CD8, CD25, and CD44. In contrast to previous investigations, no increase of thymocyte apoptosis was observed. However, T beta RII-deficient CD8(+) thymocytes displayed a 2-fold increase in proliferation rate, as determined by bromodeoxyuridine (BrdU) incorporation in vivo. These results reinforce the importance of TGF-beta as an immune regulator critical for T-cell function.