Effects of T3Rα1 and T3Rα2 gene deletion on T and B lymphocyte development
Effects of T3Rα1 and T3Rα2 gene deletion on T and B lymphocyte development
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DOI：
10.4049/jimmunol.164.1.152
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发表时间：
2000-01-01
影响因子：
4.4
通讯作者：
Marvel, J
中科院分区：
文献类型：
--
作者：
Arpin, C;Pihlgren, M;Marvel, J
甲状腺激素与T3 R α和T3 R β基因编码的几种核受体结合。现在有越来越多的证据表明甲状腺激素作用于免疫系统。事实上，缺乏甲状腺激素的小鼠表现出淋巴细胞产生的减少。然而，所涉及的机制，特别是不同的甲状腺激素受体在淋巴细胞发育中的作用尚未研究。为了解决这个问题，我们研究了T3 R α 1和T3 R α 2基因产物缺陷小鼠的淋巴细胞发育。与野生型同窝仔相比，发现脾细胞数量大幅减少，B淋巴细胞比T淋巴细胞受到更严重的影响。在骨髓中，与野生型同窝小鼠相比，在这些小鼠中发现CD 45（+）/IgM（-）pro/pre-B细胞数量减少，这种减少似乎是由于增殖缺陷，因为CD 45（+）/IgM（-）细胞在体内掺入较少的5-溴-2 '-脱氧尿苷，为了确定骨髓发育缺陷的起源，产生了T3 R α（-/-）和Rag 1（-/-）小鼠之间的嵌合动物。结果表明，对于B细胞，T3 R α 1和T3 R α 2对群体大小的控制是内在的。总之，这些结果表明T3 R α 1或T3 R α 2基因产物与B细胞库大小的控制有关。
Thyroid hormones bind to several nuclear receptors encoded by T3R alpha and T3R beta genes. There is now accumulating evidence that thyroid hormones act on the immune system. Indeed, mice deficient for thyroid hormones show a reduction in lymphocyte production. However, the mechanisms involved and, in particular, the role of the different thyroid hormone receptors in lymphocyte development have not been investigated. To address that question, we have studied lymphocyte development in mice deficient For the T3R alpha 1 and T3R alpha 2 gene products. A strong decrease in spleen cell numbers was found compared with wild-type Littermates, B lymphocytes being more severely affected than T lymphocytes. A significant decrease in splenic macrophage and granulocyte numbers was also found. In bone marrow, a reduction in CD45(+)/IgM(-) pro/pre-B cell numbers was found in these mice compared with wild-type littermates, This decrease seems to result from a proliferation defect, as CD45(+)/IgM(-) cells incorporate less 5-bromo-2'-deoxyuridine in vivo, To define the origin of the bone marrow development defect, chimeric animals between T3R alpha(-/-) and Rag1(-/-) mice were generated. Results indicate that for B cells the control of the population size by T3R alpha 1 and T3R alpha 2 is intrinsic. Altogether, these results show that T3R alpha 1 or T3R alpha 2 gene products are implicated in the control of the B cell pool size.