[en] Neuropeptide signals and specific neuropeptide receptors have been described in the thymus supporting the concept of a close dialogue between the neuroendocrine and the immune systems at the level of early T-cell differentiation. In this paper, we review recent data about neurohypophysial (NHP)-related peptides detected in the thymus from different species. We suggest that we are dealing in fact with other member(s) of the NHP hormone family, which seems to exert its activity locally through a novel model of cell-to-cell signaling, that of cryptocrine communication. This model involves exchange of signals between thymic epithelial cells and developing thymocytes. The NHP-related peptides have been shown to trigger thymocyte proliferation and could induce immune tolerance of this highly conserved neuroendocrine family.
Acher R., and Chauvet J. (1988). Structure, processing and evolution of the neurohypophysial hormone-neurophysin precursors. Biochimie 70: 1197–1207.
Al-Shawaf A.A., Kendall M.D., and Cowen T. (1991). Identification of neural profiles containing vasoactive intestinal polypeptide, acetylcholinesterase and catecholamines in the rat thymus. J. Anat. 174: 131–143.
Argiolas A., Gessa G.L., Melis M.R., Stancampiano R., and Vaccari A. (1990b). Effects of neonatal and adult thyroid dysfunction on thymic oxytocin. Neuroendocrinol. 52: 556–559.
Argiolas A., Melis M.R., Stancampiano R., Mauri A., and Gessa G.L. (1990a). Hypothalamic modulation of immunoreactive oxytocin in the rat thymus. Peptides 11: 539–543.
Burgeon E., Chapleur M., Schoenen J., Remichius D., Legros J.J., Geenen V., and Robert F. (1991). Monoclonal antibodies to oxytocin: Production and characterization. J. Neuroimmunol. 31: 235–244.
D’Andrea V., Artico M., Capuano L., Gallottini L., and Ambrogi V. (1989). Dimostrazione immunoistochimica del neuropeptide Y nel timo umano normale e nel timoma. Medicina (Florence) 9: 299–301.
Elands J., Barberis C., and Jard S. (1988b). [3H]-[Thr4, Gly7] OT: A highly selective ligand for central and peripheral OT receptors. Am. J. Physiol. 254: E31–E38.
Elands J., Resink A., and De Kloet E.R. (1988a). Oxytocin receptors in the rat thymic gland. Eur. J. Pharmacol. 151: 345–346.
Elands J., Resink A., and De Kloet E.R. (1990). Neurohypophyseal hormone receptors in the rat thymus, spleen, and lymphocytes. Endocrinology 126: 2703–2710.
Ericsson A., Geenen V., Robert F., Legros J.J., Vrindts-Gevaert Y., Franchimont P., Brene S., and Persson H. (1990). Expression of preprotachykinin-A and neuropeptide-Y messenger RNA in the thymus. Molec. Endocrinol. 4: 1211–1218.
Ervin M.G., Leake R.D., Ross M.G., Calvario G.C., and Fischer D.A. (1985). Arginine vasotocin in ovine fetal blood, urine, and amniotic fluid. J. Clin. Invest. 75:1696–1701.
Ervin M.G., Polk D.H., Humme J.A., Ross M.G., Leake R.D. and Fischer D.A. (1988). Immunoreactive vasotocin, vasopressin and oxytocin in ovine fetal and neonatal thymus glands. Clin. Res. 36: 217A.
Felten D.L., Felten S.Y., Carlson S.L., Olschowska J.A., and Livnat, S. (1985). Noradrenergic and peptidergic innervation of lymphoid tissue. J. Immunol. 135: 755s–765s.
Flint A.P.F., Leat W.M.F., Sheldrick E.L., and Stewart H.J. (1986). Stimulation of phosphoinositide hydrolysis by oxytocin and the mechanism by which oxytocin controls prostaglandin synthesis in the ovine endometrium. Biochem. J. 237:797–805.
Fuller, P.J., and Verity K. (1989). Somatostatin gene expression in the thymus gland. J. Immunol. 143: 1015–1017.
Geenen V., Defresne, M.P., Legros J.J., Franchimont P., and Boniver J. (1988a). The neurohormonal thymic microenvironment: Immunocytochemical evidence that thymic nurse cells are neuroendocrine cells. Neuroendocrinol. 47: 365–368.
Geenen V., Legros J.J., Franchimont P., Baudrihaye M., Defresne M.P. and Boniver J. (1986). The neuroendocrine thymus: Coexistence of oxytocin and neurophysin in the human thymus. Science 232: 508–511.
Geenen V., Legros J.J., Franchimont P., Defresne M.P., Boniver J., Ivell R., and Richter D. (1987). The thymus as a neuroendocrine organ: Synthesis of vasopressin and oxytocin in human thymic epithelium. Ann. N.Y. Acad. Sci. 496: 56–66.
Geenen V., Legros J.J., Hazee-Hagelstein M.T., Louis-Kohn F., Lecomte-Yerna M.J., Demoulin A., and Franchimont, P. (1985). Release of immunoreactive oxytocin and neurophysin I by cultured luteinizing bovine granulosa cells. Acta Endocrinol. (Copenhagen) 110: 263–270.
Geenen V., Robert F., Fatemi M., Defresne M.P., Boniver J., Legros J.J., and Franchimont P. (1988b). Vasopressin and oxytocin: Thymic signals and receptors in T cell ontogeny. In: Recent progress in posterior pituitary hormones, Yoshida S. and Share L. Eds. (New York: Elsevier), pp. 303–310.
Geenen V., Martens H., Robert F., Legros J.J., Defresne M.P., Boniver J., Martial J., Lefèbvre P.J. and Franchimont P. (1991a). Thymic cryptocrine signaling and the immune recognition of self neuroendocrine functions. Prog. NeuroendocrinImmunol. 4:135–142.
Geenen V., Robert F., Martens H., Benhida A., De Giovanni G., Defresne M.P., Boniver J., Legros J.J., Martial J., and Franchimont P. (1991a). Biosynthesis and paracrine/cryptocrine actions of neurohypophysial-related peptides in the thymus. Mol. Cell. Endocrinol. 76: C27–C31.
Geppetti P., Frilli S., Renzi D., Santicioli P., Maggi C.A., Theodorsson E., and Fanciullacci M. (1989). Distribution of calcitonin gene-related peptide-like immunoreactivity in various rat tissues: Correlation with substance P and other tachykinins and sensitivity to capsaicin. Regul. Pept. 23: 289–298.
Geppetti P., Maggi C.A., Zecchi-Orlandini S., Santicioli P., Meli A., Frilli S., Spillantini M.G., and Amenta F. (1987). Substance P-like immunoreactivity in capsaicin-sensitive structures of the rat thymus. Regul. Pept. 18:312–329.
Geppetti P., Theodorsson-Norheim E., Ballerini G., Alessandri M., Maggi C.A., Santicioli P., Amenta F., and Fanciullacci M. (1988). Capsaicin-sensitive tachykinin-like immunoreactivity in the thymus of rats and guinea-pigs. J. Neuroimmunol. 19: 3–9.
Giraud F., Fabien N., Auger C., Girod C., Loire R., and Monier J.C. (1990). Human epithelial thymic tumours: Heterogeneity in immunostaining of epithelial cell markers and thymic hormones. Thymus 15:15–29.
Gomariz R.P., Lorenzo M.J., Cacicedo L., Licente A., and Zapata A.G. (1990). Demonstration of immunoreactive vasoactive intestinal peptide (IR-VIP) and somatostatin (IR-SOM) in rat thymus. Brain Behav. Immun. 4:151–161.
Haynes B.F., Shimizu K., and Eisenbarth G.S. (1983). Identification of human and rodent thymic epithelium using tetanus toxin and monoclonal antibody A2B5. J. Clin. Invest. 71: 9–14.
Herbst W.M., Kummer W., Hofmann W., Otto H., and Heym C. (1987). Carcinoid tumors of the thymus. An immunohistochemical study. Cancer 60: 2465–2470.
Hunt N.H., Perris A.D., and Sandford P.A. (1977). Role of vasopressin in the mitotic response of rat bone marrow cells to haemorrhage. J. Endocrinol. 72: 5–16.
Ivell R., and Richter D. (1984). Structure and comparison of the oxytocin and vasopressin genes from the rat. Proc. Natl. Acad. Sci. USA 81: 2006–2010.
Jard S., Gaillard R.C., Guillon G., Marie J., Schoenenberg P., Muller A.F., Manning M., and Sawyer W.H. (1986). Vasopressin antagonists allow demonstration of a novel type of vasopressin receptor in the rat adenohypophysis. Molec. Pharmacol. 30:171–177.
Jevremovic M., Barbijeri M., Kovacevic D., Arambasic M., Kartaljevic G., Natalic D.J., and Pazin S. (1990). Identification of neuroendocrine oxytocic activity of the human fetal thymus. Thymus 15:181–185.
Kurihara M., Katamine S., and Saavedra J.M. (1987). Atrial natriuretic peptide, ANP (99-126), receptors in rat thymocytes and spleen cells. Biochem. Biophys. Res. Commun. 145:789–796.
Land H., Grez M., Ruppert S., Schmale H., Rehbein N., Richter D., and Schuetz G. (1983). Deduced amino acid sequence from the bovine oxytocin-neurophysin I precursor cDNA. Nature 302: 342–344.
Land H., Schuetz G., Schmale H., and Richter D. (1982). Nucleotide sequence of cloned cDNA encoding bovine arginine vasopressin-neurophysin II precursor. Nature 295: 299–303.
Le P.T., Denning S.M., Haynes B.F., and Singer K.H. (1990). Thymic epithelial-cell-derived cytokines and their roles in thymic precursor cell differentiation. Res. Immunol. 141: 271–275.
Legros J.J. (1975). The radioimmunoassay of human neurophysins: Contribution to the understanding of the physiopathology of neurohypophyseal function. Ann. N.Y. Acad. Sci. 248: 281–303.
Legros J.J., and Ansseau M. (1989). Increased basal plasma vasopressin-neurophysin in mania. Horm. Res. 31:55–58.
Legros J.J., Louis F., Demoulin A., and Franchimont P. (1976). Immunoreactive neurophysins and vasotocin in human foetal pineal glands. J. Endocrinol. 69: 289–294.
Lorenz R.G., and Allen P.M. (1989). Thymic cortical epithelial cells can present self-antigens in vivo. Nature 337: 560–562.
Lorton D., Bellinger D.L., Felten S.Y., and Felten, D.L. (1990). Substance P innervation of the rat thymus. Peptides 11: 1269–1275.
Maggi M., Malowzowski S., Kassis S., Guardabasso V., and Rodbard D. (1987). Identification and characterization of two classes of receptors for oxytocin and vasopressin in porcine tunica albuginea, epididymis, and vas deferens. Endocrinol. 120: 986–994.
Marchetti B., Guarcello V., Morale M.C., Bartoloni G., Farinella Z., Cordaro S., and Scapagnini U. (1989). Luteinizing hormone-releasing hormone-binding sites in the rat thymus: Characteristics and biological function. Endocrinology 125:1025–1036.
Markwick A.J., Lolait S.J., and Funder J.W. (1986). Immunoreactive arginine vasopressin in the rat thymus. Endocrinology 119:1690–1696.
Marrack P., McCormack J., and Kappler J. (1989). Presentation of antigen, foreign major histocompatibility complex proteins and self by thymus cortical epithelium. Nature 338: 503–505.
Martens H., Robert F.R., Legros J.J., Geenen V., and Franchimont P. (1992). Expression of functional neurohypophysial peptide receptors by murine immature and cytotoxic T cell lines. Prog. NeuroEndocrinImmunol., in press.
Michell R.H., Kirk C.J. and Billah M.M. (1979). Hormonal stimulation of phosphatidylinositol breakdown, with particular reference to the hepatic effects of vasopressin. Biochem. Soc. Trans. 7: 861–865.
Morley S.D., Schönrock C., Heierhorst J., Figueroa J., Lederis K., and Richter D. (1990). Vasotocin genes of the teleost fish Catostomus commersoni: Gene structure, exon-intron boundary, and hormone precursor organization. Biochemistry 29: 2506–2511.
Nicolas J.F., Reano A., Kaiserlian D., and Thivolet J. (1989). Epithelial cell heterogeneity in mammalian thymus: Monoclonal antibody to high molecular weight keratins exclusively binds to Hassall’s corpuscles. Histochem. J. 21: 357–364.
Nieuwenhuis J.J. (1984). Arginine vasotocin (AVT), an alleged hormone of the mammalian pineal gland. Life Sci. 35: 1713–1724.
Pavel S. (1975). Vasotocin biosynthesis by neurohypophysial cells from human fetuses. Evidence for its ependydimal origin. Neuroendocrinol. 19:150–156.
Pavel S., Goldstein R., and Calb M. (1975). Vasotocin content in the pineal gland of foetal, newborn and adult male rats. J. Endocrinol. 66: 283–289.
Piantelli M., Maggiano N., Larocca L.M., Ricci R., Ranelletti F.O., Lauriola L., and Capelli A. (1990). Neuropeptideimmunoreactive cells in human thymus. Brain Behav. Immun. 4:189–197.
Ransom J., Wu R., Fischer M., and Zlotnik A. (1991). Antigen presenting ability of thymic macrophages and epithelial cells: evidence for defects in the antigen processing function of thymic epithelial cells. Cell. Immunol. 134:180–190.
Richter, D., and Schmale H. (1984). Vasopressin expression in normal and diabetes insipidus (Brattleboro) rats. Trends Neurosci. 7: 317–319.
Robert F., Geenen V., Schoenen J., Burgeon E., De Groote D., Defresne M.P., Legros J.J. and Franchimont P. (1991). Colocalization of immunoreactive oxytocin, vasopressin and interleukin-1 in human thymic epithelial neuroendocrine cells. Brain, Behavior and Immunity 5:102–115.
Robert F., Léon-Henri B.P., Chapleur-Chateau M.M., Girr M.N., and Burlet A.J. (1985). Comparison of three immunoassays in the screening and characterization of monoclonal antibodies against arginine-vasopressin. J. Neuroimmunol. 9: 205–220.
Rozengurt E. (1986). Early signals in the mitogenic response. Science 234:161–166.
Savino W., and Dardenne M. (1984). Thymic hormone-containing cells VI. Immunohistologic evidence for simultaneous presence of thymulin, thymopoietin and thymosin α1 in normal and pathological human thymuses. Eur. J. Immunol. 14: 987–991.
Scherbaum W.A., and Bottazzo G.F. (1983). Autoantibodies to vasopressin cells in idiopathic diabetes insipidus: Evidence for an autoimmune variant. Lancet 1: 897–901.
Shigematsu K., Saavedra J.M., and Kurihara M. (1986). Specific substance P binding sites in rat thymus and spleen: In vitro autoradiographic study. Regul. Pept. 16:147–156.
Smith A., and McIntosh N. (1983). Neurohypophyseal peptides in the human fetus: Presence in pituitary extracts of immunoreactive arginine vasotocin. J. Endocrinol. 99: 441–445.
Smitz S., Legros J.-J., Franchimont P., and Le Maire M. (1988). Identification of vasopressin-like peptides in the plasma of a patient with the syndrome of inappropriate secretion of antidiuretic hormone and oat cell carcinoma. Acta Endocrinol. (Copenhagen) 119: 567–574.
Söder O., and Hellström P.M. (1989). The tachykinins neurokinin A and physalaemin stimulate murine thymocyte proliferation. Int. Arch. Allergy Appl. Immunol. 90: 91–96.
Sundler F., Carraway R.E., Hakanson R., Alumets J., and Dubois M.P. (1978). Immunoreactive neurotensin and somatostatin in the chicken thymus. Cell Tiss. Res. 194: 367–376.
Vollmar A.M., and Schulz R. (1990). Atrial natriuretic peptide is synthesized in the human thymus. Endocrinology 126: 2277–2280.
Von Gaudecker B., Steinmann G.G., Hansmann M.L., Harpprecht J., Milicevic N.M., and Muller-Hermelink H.K. (1986). Immunohistochemical characterization of the thymic microenvironment. A light-microscopic and ultrastructural immunocytochemical study. Cell Tissue Res. 244: 403–412.
Webb S.R., and Sprent J. (1990). Tolerogenicity of thymic epithelium. Eur. J. Immunol. 20: 2525–2528.
Weihe E., Muller S., Fink T., and Zentel H.J. (1989). Tachykinins, calcitonin gene-related peptide and neuropeptide Y in nerves of the mammalian thymus: Interactions with mast cells in autonomic and sensory neuroimmunomodulation? Neurosci. Lett. 100: 77–82.
Wekerle H., and Ketelsen, U.P. (1980). Thymic nurse cells. Iabearing epithelium involved in T-lymphocyte differentiation? Nature 283: 402–404.
Whitfield J.F., MacManus J.P., and Gillan D.J. (1970). The possible mediation by cyclic AMP of the stimulation of thymocyte proliferation by vasopressin and the inhibition of this mitogenic action by thyrocalcitonin. J. Cell Physiol. 76: 65–76.