[en] Thymic epithelial cell physiology is known to be under neuroendocrine control. In particular, thyroid hormones modulate thymic hormone secretion by thymic epithelial cells in vivo and in vitro, thus suggesting the existence of specific receptors for those hormones in this component of the thymic microenvironment. Yet, thyroid hormone-binding sites have previously been detected only in crude thymus fractions and lymphocytes. We, thus, decided to search for T3 receptors in the thymic epithelium, by using an antinuclear T3 receptor monoclonal antibody. In situ immunohistochemical analysis of thymic frozen sections showed nuclear labeling of both lymphoid and nonlymphoid cells in the cortex and medulla. Moreover, in vitro studies using thymic epithelial cell lines and the so-called thymic nurse cells revealed a positive reaction in the chromatin, with nucleoli remaining negative. Immunoblot data clearly showed a single protein band of 57K reactive with the antinuclear T3 receptor antibody in murine thymus extracts as well as in the thymic epithelial cell lines. Lastly, in vitro treatment of these cells with T3 resulted in a transient, yet profound, down-modulation of the receptor. In conclusion, our findings provide molecular evidence that the action of thyroid hormones on thymic epithelium occurs via the typical 57K nuclear T3 receptors.
Villa-Verde, D M; Department of Immunology, Federal University of Rio de Janeiro, Brazil
Defresne, Marie-Paule ; Université de Liège - ULiège > Département des sciences précliniques MI > Histologie - Cytologie
Vannier-dos-Santos, Marcos A.; Laboratory of Ultrastructure and Electron Microscopy, Institute for Byophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Dussault, Jean H.; Unite de Recherche en Ontogenese et Genetique Moleculaires, Universite Laval, QC, Canada
Boniver, Jacques ; Université de Liège - ULiège > Département des sciences précliniques MI > Anatomie et cytologie pathologiques
Savino, Wilson; Laboratory on Thymus Research, Department of Immunology, Institute Oswaldo Cruz, Rio de Janeiro, Brazil
Language :
English
Title :
Identification of nuclear triiodothyronine receptors in the thymic epithelium.
Savino W, Dardenne M, Papiernik M, Bach JF 1982 Thymic hormone containing cells. Characterization and localization of serum thymic factor in young mouse thymus studied by monoclonal antibodies. J Exp Med 156:628-633
Savino W, Dardenne M 1984 Thymic hormone containing cells. VI. Immunohistologic evidence for the simultaneous presence of thymulin, thymopoietin and thymosin or-1 in normal and pathological human thymuses. Eur J Immunol 14:984-991
Savino W, Dardenne M, Bach JF 1983 Thymic hormone containing cells. III. Evidence for a feed-back regulation on the secretion of the serum thymic factor (FTS) by thymic epithelial cells. Clin Exp Immunol 52:7-12
Cohen S, Berrih S, Dardenne M, Bach JF 1986 Feed-back regulation of the secretion of a thymic hormone (thymulin) by human thymic epithelial cells in culture. Thymus 8:109-119
Dardenne M, Savino W1990 Neuroendocrine control of the thymic epithelium: modulation of thymic endocrine function, cytokeratin expression and cell proliferation by hormones and neuropeptides. Prog Neuroendocrineimmunol 3:18-25
Geenen V, Martens H, Robert F, Legros JJ, Defresne MP, Boniver J, Martial J, Lefebvre PJ, Franchimont P 1991 Thymic cryptocrine signalling and the immune recognition of self neuroendocrine functions. Prog Neuroendocrineimmunol 4:135-142
Dardenne M, Itoh T, Homo-Delarche F 1986 Presence of glucocorticoid receptors in cultured thymic epithelial cells. Cell Immunol 100:112-118
Grossman CJ, Nathan P, Taylor BB, Sholiton LJ 1979 Rat thymic dihydrotestosterone receptor. Preparation, location and physiological properties. Steroids 34:533-539
Grossman CJ, Sholiton J, Nathan P 1979 A rat thymic estrogen receptor. I. Preparation, location and physiological properties. J Steroid Biochem 11:1233-1240
Pearce PT, Khalid BA, Funder JW 1983 Progesterone receptors in rat thymus. Endocrinology 113:1287-1292
Ban E, Gagnerault MC, Jammes H, Postel-Vinay MC, Haour F, Dardenne M 1991 Specific binding sites for growth hormone in cultured mouse thymic epithelial cells. Life Sri 48:2141-2148
Dardenne M, Kelly P, Bach JF, Savino W 1991 Identification of functional prolactin receptor in thymic epithelial cells. Proc Natl Acad Sci USA 88:9700-9704
Csaba G, Sudar F, Dobozy O 1977 Triiodothyronine receptors in lymphocytes of newborn and adult rats. Horm Metab Res 9:499-501
Segal J, Ingbar SH 1982 Specific binding sites for triiodothyronine in the plasma membrane of rat thymocytes. Correlation with biochemical response. J Clin Invest 70:919-926
Brtko J, Knopp J 1985 Specific receptors for thyroxine in nuclear non-histone proteins of rat thymus during early, medium and late period of life. Exp Clin Endocrinol 86:317-322
Galton VA, St Germain DL, Whittemore S 1986 Cellular uptake of 3,5,3′-triiodothyronine and thyroxine by red blood and thymus cells. Endocrinology 118:1918-1923
Savino W, Wolf B, Aratan-Spire S, Dardenne M 1984 Thymic hormone containing cells. IV. Fluctuations in the thyroid hormone levels in vivo can modulate the secretion of thymulin by the epithelial cells of young mouse thymus. Clin Exp Immunol 55:629-635
Dardenne M, Savino W, Bach JF 1988 Modulation of thymic endocrine function by thyroid and steroid hormones. Int J Neurosci 39:325-334
Scheiff JM, Cordier AC, Haumont S 1977 Epithelial cell proliferation in thymic hyperplasia induced by triiodothyronine. Clin Exp Immunol 27:516-521
Fabris N, Mocchegiani E, Mariotti S, Pacini F, Pinchera A 1986 Thyroid function modulates thymic endocrine activity. J Clin Endocrinol Metab 62:474-478
Luo M, Faure R, Ruel J, Dussault JH 1988 A monoclonal antibody to the rat nuclear triiodothyronine receptor: production and characterization. Endocrinology 123:180-186
Itoh T, Doi H, Kasahara S, A mouse thymic epithelial cell line. Its establishment, identification, functions. 6th International Congress of Immunology, Toronto, Ontario, Canada, 1986, p 27 (Abstract)
Itoh T, Aizu S, Kasahara S, Mori T 1981 Establishment of a functioning epithelial cell line from the rat thymus. A cell line that induces the differentiation of rat bone marrow cells into T cell lineage. Biomed Res 2:11-19
Wekerle H, Ketelsen UP 1980 Thymic nurse cells-Ia-bearing epithelium involved in T-lymphocyte differentiation? Nature 283:402-404
Houben-Defresne MP, Varlet A, Goffinet G, Boniver J 1982 Thymic nurse cells are the first site of virus replication after inoculation of the radiation leukemia virus. Leukemia Res 6:231-241
Bendayan M, Nanci A, Yan F, W, K 1987 Effect of tissue processing on colloidal gold cytochemistry. J Histochem Cytochem 35:983-996
Savino W, Dardenne M 1988 Immunohistochemical studies on a human thymic epithelial cell subset difined by the anti-cytokeratin 18 monoclonal antibody. Cell Tissue Res 254:225-231
Lannes-Vieira J, Dardenne M, Savino W 1991 Extracellular matrix components of the mouse thymus microenvironment. Ontogenetic studies and modulation by glucocorticoid hormones. J Histochem Cytochem 39:1539-1546
Kyewski BA, Kaplan HS 1982 Lymphoepithelial interactions in the mouse thymus: phenotypic and kinetic studies on thymic nurse cells. J Immunol 128:2287-2294
Boyd RL, Oberhuber G, Hala K, Wick G 1984 Obese strain (OS) chickens with spontaneous autoimmune thyroiditis have a deficiency in thymic nurse cells. J Immunol 132:718-724
Luo M, Faure R, Tong YA, Dussault JH 1989 Immunocytochemical localization of nuclear 3,5,3'-triiodothyronine receptor in the adult rat: liver, kidney, heart, lung and spleen. Acta Endocrinol (Copenh) 120:451-458
Horowitz ZD, Sahnoun H, Pascual A, Casanova J, Samuels HH 1988 Analysis of photoaffinity label derivatives to probe thyroid hormone receptor in human fibroblasts, GHi cells, and soluble receptors preparations. J Biol Chem 263:6636-6642
Tagami T, Nakamura H, Sasaki S, Mori T, Yoshioka H, Yoshida H, Imura H 1990 Immunohistochemical localization of nuclear 3,5,3′-triiodothyronine receptor proteins in rat tissues studied with antiserum against c-erb A/T3 receptor. Endocrinology 127:1727-1734
Macchia E, Nakai A, Janiga A, Sakurai A, Fisfalen ME, Gardner P, Soltani K, DeGroot LJ 1990 Characterization of site-specific polyclonal antibodies to c-erb A peptides recognizing human thyroid hormone receptors a1α2 and β and native 3,5,3′-triiodothyronine receptor, and study of tissue distribution of the antigen. Endocrinology 126:3232-3239
Bernal J, Coleoni AH, DeGroot LJ 1978 Thyroid hormone receptors from liver nuclei: characteristics of receptor from normal, thyroid- ectomized, and triiodothyronine-treated rats; measurement of occupied and unoccupied receptors, and chromatin binding receptors. Endocrinology 103:403-413
Williams GR, Franklyn JA, Sheppard MC 1991 Thyroid hormone and glucocorticoid regulation of receptor and target gene mRNAs in pituitary GH3 cells. Mol Cell Endocrinol 80:127-138
Hodin RA, Lazar MA, Wintman BI, Darling DS, Koenig RJ, Larsen PR, Moore DD, Chin WW 1989 Identification of a thyroid hormone receptor that is pituitary-specific. Science 244:76-79
Dussault JH, Labrie F 1975 Development of the hypothalamic- pi tuitary-thyroid axis in the neonatal rat. Endocrinology 97:1321-1324
Segal J, Ingbar SH 1979 Stimulation by triiodothyronine of the in vitro uptake of sugars by rat thymocytes. J Clin Invest 63:507-515
Villa-Verde D, M, S, Defresne MP, Greimers R, Dardenne M, Savino W, Boniver J 1991 Induction of thymocyte proliferation by supernatants from a mouse thymic epithelial cell line. Cell Immunol 136:113-121
Fabris N, Mocchegiani E 1985 Endocrine control of thymic serum factor production in young-adult and old mice. Cell Immunol 91:325-335
Fabris N, Mocchegiani E, Mariotti S, Pacini F, Pinchera A 1989 Thyroid-thymus interactions during development and aging. Horm Res 31:85-89