Effects of T3Rα1 and T3Rα2 Gene Deletion on T and B Lymphocyte Development

Abstract

Thyroid hormones bind to several nuclear receptors encoded by T3Rα and T3Rβ 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 T3Rα1 and T3Rα2 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 T3Rα−/− and Rag1−/− mice were generated. Results indicate that for B cells the control of the population size by T3Rα1 and T3Rα2 is intrinsic. Altogether, these results show that T3Rα1 or T3Rα2 gene products are implicated in the control of the B cell pool size.