title: Effects of T3R alpha 1 and T3R alpha 2 gene deletion on T and B lymphocyte development.
abstract: 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.
authors.affiliation: Ecole Normale Supérieure de Lyon, Laboratoire de Biologie Moléculaire et Cellulaire, Unité Mixte de Recherche 5665, Centre National de la Recherche Scientifique/Ecole Normale Supérieure, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Arpin
authors.forename: M
authors.initials: M
authors.lastname: Pihlgren
authors.forename: A
authors.initials: A
authors.lastname: Fraichard
authors.forename: D
authors.initials: D
authors.lastname: Aubert
authors.forename: J
authors.initials: J
authors.lastname: Samarut
authors.forename: O
authors.initials: O
authors.lastname: Chassande
authors.forename: J
authors.initials: J
authors.lastname: Marvel
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D001854:Bone Marrow Cells / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D004254:DNA Nucleotidyltransferases / Q000172:deficiency / Q000235:genetics; D017353:Gene Deletion; D019426:Integrases; D018655:Lymphocyte Count; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000502:physiology; D045522:Recombinases; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013234:Stem Cells / Q000473:pathology; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: D011988:Receptors, Thyroid Hormone; D045522:Recombinases; D014284:Triiodothyronine; D004254:DNA Nucleotidyltransferases; D019426:Integrases; C115006:integron integrase IntI1