Role of Thymosin and the Neuroendocrine System in the Regulation of Immunity

  • Nicholas R. Hall
  • Allan L. Goldstein


A central role for the thymus in host defense has been documented by studies correlating either surgical or genetic absence of this gland with immunodeficiency. Consequently, thymic immunity has become synonymous with cellular immunity, a component of host defense that interfaces with both phagocytic and immunoglobulin producing cells.


Terminal Deoxynucleotidyl Transferase Neuroendocrine System Thymic Epithelial Cell Thymus Gland Thymic Hormone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Ahlqvist, J., 1981, Outline of endocrine influences on immune processes, in: “Psychoneuroimmunology”, R. Ader, ed., Academic Press New York.Google Scholar
  2. Ahmed, A., Smith, A.H., Wong, D.M., Thurman, G.B., Goldstein, A.L. and Sell, K.W., 1978, In vitro induction of Lyt surface markers on precursor cells incubated with thymosin polypeptides, Cancer Treat. Rep., 62:1739.PubMedGoogle Scholar
  3. Ahmed, A., Wong, D.M., Thurman, G.B., Low, T.L.K., Goldstein, A.L., Sharkis, S.J., and Goldschneider, I., 1979, T-lymphocyte maturation: Cell surface markers and immune function induced by T-lymphocyte cell free products and thymosin polypeptides, Ann. N.Y. Acad. Sci., 332:81.PubMedCrossRefGoogle Scholar
  4. Andersen, D.H., 1932, The relationship between the thymus and reproduction, Physiol. Rev., 12:1.Google Scholar
  5. Asherson, G.B., Sembala, M., Nayhew, B. and Goldstein, A.L., 1976, Adult thymectomy: prevention of the appearance of suppressor T cells which depress contact sensitivity to picryl chloride and reversal of adult thymectomy effect by thymus extract, Eur. J. Immunol., 6:699.PubMedCrossRefGoogle Scholar
  6. Bach, J.F., Duval, D., Dardenne, M., Solomon, J.C., Tursz, T. and Fournier, C., 1975, The effects of steroids on T cells, Transplant. Proc., 7: 25.PubMedGoogle Scholar
  7. Bach, J.F., Dardenne, M., Pleau, J.M. and Rosa, J., 1977, Biochemical characterization of serum thymic factor, Nature, 266:55.PubMedCrossRefGoogle Scholar
  8. Belokrylov, G.A., Morozov, V.G. and Khavinson, K.H., 1979, Effect of substances of polypeptide nature isolated from the cerebral cortex on the immune response in mice, Bull. Exp. Biol. Med., 86:1631.Google Scholar
  9. Bernardi G. and Comsa, J., 1965, Purification chromatographique d’une preparation de thymus donée d’activité hormonale, Experientia, 21: 416.PubMedCrossRefGoogle Scholar
  10. Besedovsky, H.O. and Sorkin, E., 1974, Thymus involvement in female sexual maturation, Nature, 249:356.PubMedCrossRefGoogle Scholar
  11. Besedovsky, H.O. and Sorkin, E., 1977, Network of immune-neuroendocrine interactions, Clin. Exp. Immunol., 27:1.PubMedGoogle Scholar
  12. Besedovsky, H.O., Del Rey, A. and Sorkin E., 1981, Lymphokine-containing supernatants from Con-A-stimulated cells increase corticosterone blood levels, J. Immunol., 126:385.PubMedGoogle Scholar
  13. Biggar, W.D., Park, B.H. and Good, R.A., 1973, Immunologic reconstitution, Ann. Rev. Med., 24:135.PubMedCrossRefGoogle Scholar
  14. Billingsley, M.L., Hall, N.R. and Mandel, H.G., 1981, Immunosuppression blocks trauma induced neuroglial DNA synthesis in the rat, Fed. Proc., 40:526.Google Scholar
  15. Bleier R., and Algrecht, R., 1980, Supraependymal macrophages of third ventricle of hamster: Morphological, functional and histochemical characterization in “situ” and in culture, J. Comp. Neurol., 192:489.PubMedCrossRefGoogle Scholar
  16. Bruley-Rosset, M., Florentin, I., Kiger, N., Schulz, J., Davigny, M. and Mathé, G., 1979, in: “The immune system, functions and therapy of dysfunction,” H. Faraitre, ed., Academic Press, New York.Google Scholar
  17. Comsa, J., 1971, Thymic hormones, Hormones, 2:226.PubMedCrossRefGoogle Scholar
  18. Craddock, D.G., 1978, Corticosteriod-induced lymphopenia, immunosuppression and body defense, Ann. Int. Med., 88:564.PubMedGoogle Scholar
  19. Dabrowski, M.P., and Goldstein, A.L., 1976, Thymosin induced changes in cell cycle of lymphocytes, from aging neonatally thymectomized rats, Immunol. Commun., 5:695.PubMedGoogle Scholar
  20. D’Agostaro, G., Frasca, D., Garavini, M. and Doria, G., 1980, Immunorestoration of old mice by injection of thymus extract; enhancement of T-cell, T-cell cooperation in the in vitro antibody response, Cell. Immunol., 53:207.PubMedCrossRefGoogle Scholar
  21. Dalmasso, A.P., Martinez, C., Sjodin, K., and Good, A., 1963. Studies on the role of the thymus in immunology. Reconstitution of immunologic capacity in mice thymectomized at birth, J. Exp. Med., 118:1089.PubMedCrossRefGoogle Scholar
  22. Dauphinée, M.J., Talal, N., Goldstein, A L. and White, A., 1974, Thymosin corrects the abnormal DNA synthetic response of NZB mouse thymocytes, Proc. Natl. Acad. Sci., 71:2637.PubMedCrossRefGoogle Scholar
  23. Davies, A.J.S., 1969, The thymus and the cellular basis of immunity, Transplant. Rev., 1:43.PubMedGoogle Scholar
  24. Deschaux, P., Massengo, and Fontanges, R., 1979, Endocrine interaction of the thymus with the hypophysis, adrenals and testes: effects of two thymic extracts, Thymus, 1:95.PubMedGoogle Scholar
  25. Dumonde, D.C., Pulley, M.S., Hamblin, A.S Singh, A.K., Southcott, B. M., O’Connell, D., Paradinas, F.J., Robinson, M.R.G., Rigby, C.C., Hollander, F. den, Schurs, A., Verheul, H. and Vliet, E. van, Short term and long term administration of lymphoblastoid cell line lymphokine (LVL-LK) to patients with advanced cancer, in: “Lymphokines and Thymic Hormones: Their Potential Utilization in Cancer Therapeutics,” A.L. Goldstein and M.A. Chirigos, eds., Raven Press, in press.Google Scholar
  26. East, J. and Parrott, D.M.V., 1964, Prevention of wasting in mice thymectomized at birth and their subsequent rejection of allogeneic leukemic cells, J. Natl. Cancer Inst., 33:673.PubMedGoogle Scholar
  27. Fontana, A., Grieder, A., Arrenbrecht, S.T. and Grob, P., 1980, “In vitro” stimulation of glia cells by a lymphocyte-produced factor, J. Neurological Sci., 46:55.CrossRefGoogle Scholar
  28. Gershwin, M.E., Ahmed, A., Steinberg, A.D., Thurman, G.B. and Goldstein, A.L., 1974, Correction of T-cell function by thymosin in New Zealand mice, J. Immunol., 113:1068.PubMedGoogle Scholar
  29. Gershwin, M.E., Kruise, W. and Goldstein G., 1979, The effect of thymopoietin 32=36 and ubiquitin on spontaneous immunopathology of New Zealand mice, J. Rheumatol., 6:610.PubMedGoogle Scholar
  30. Goldschneider, I., Ahmed, A., Bollum, F.J. and Goldstein, A.L.,1981, Induction of terminal deoxynucleotidyl transferase and Lyt antigens with thymos in: Identification of multiple subsets of prothymocytes in mouse bone marrow and spleen, Proc. Natl. Acad. Sci., 78:2469.PubMedCrossRefGoogle Scholar
  31. Goldstein, A.L., Slater, F.D. and White, A., 1966, Preparation, assay and partial purification of a thymic lymphocytopoietic factor (Thymosin), Proc. Natl. Acad. Sci., 56:1010.PubMedCrossRefGoogle Scholar
  32. Goldstein, A.L., Guha, A., Zatz, M.M. and White, A., 1972, Purification and biological activity of thymosin, a hormone of the thymus gland, Proc. Natl. Acad. Sci., 69:1800.PubMedCrossRefGoogle Scholar
  33. Goldstein, G., Scheid, M., Hammerling, U., Boyse, E.A., Schlesinger, D.H. and Nial, H.D., 1975, Isolation of a polypeptide that has lymphocyte-differentiating properties and is probably represented universally in living cells, Proc. Natl. Acad. Sci., 72:11.PubMedCrossRefGoogle Scholar
  34. Goldstein, A.L., Low, T.L.K., McAdoo, M., McClure, J., Thurman, G. B., Rossio, J.L., Lai, C-y, Chang, D., Wang, S-S., Harvey, C., Ramel, A.H., and Meienhofer, J., 1977, Thymosin α1: Isolation and sequence analysis of an immunologically active thymic polypeptide, Proc. Natl. Acad. Sci., 74:725.PubMedCrossRefGoogle Scholar
  35. Goldstein, A.L., Thurman, G.B., Low, T.L.K., Rossio, J.L. and Trivers, G.E., 1978, Hormonal influences on the reticuloendothelial system. Current status of the role of thymosin in the regulation and modulation of immunity, J. Reticuloend. Soc., 23:252.Google Scholar
  36. Goldstein, A.L., Low, T.L.K., Thurman, G.B., Zatz, M.M., Hall, N.R. Chen, C-P., Hu, S-K., Naylor, P.B. and McClure, J.E., 1981, Current status of thymosin and other hormones of the thymus gland, Recent Progress in Hormone Res., in press.Google Scholar
  37. Goldstein, G., Lau, C.Y., 1980, Immunoregulation by thymopoietin., J. Supramol. Struct., 14:397.PubMedCrossRefGoogle Scholar
  38. Hall, N.R., 1980, Neural control of immunogenesis, in: Molecular and behavioral neuroendocrinology. C.B., Nemeroff and A.J. Dunn, eds., Spectrum, N.Y., in press.Google Scholar
  39. Hall, N.R. and Goldstein, A.L., 1981, Endocrine regulation of host immunity: the role of steroids and thymosins, in: “Immunogeni-city,” F. Borek, ed., Elsevier Press, Holland, in press.Google Scholar
  40. Hall, N.R. and Luttge, W.G., 1977, Diencephalic sites responsive to prostaglandin E2: facilitation of sexual receptivity in estrogen primed, ovariectomized rats, Brain Res. Bull., 2:203.PubMedCrossRefGoogle Scholar
  41. Hall, N.R., Luttge, W.G. and Berry, R.B., 1975, Intracerebral prostaglandin E2: Effects upon sexual behavior, open-field activity and body temperature in ovariectomized female rats, Prostaglandins, 10:177.Google Scholar
  42. Hall, N.R., Palaszynski, E.W., Moody, T.W. and Goldstein, A.L., 1981, Evidence for a CNS-thymus axis involving thymosin peptides, Soc. for Neuroscience, abstract.Google Scholar
  43. Harms, P.G., Ojeda, S.R., and McCann, S.M., 1973, Prostaglandin involvement in hypothalamic control of gonadotropin and prolactin release, Science, 181:760.PubMedCrossRefGoogle Scholar
  44. Hays, E.F., 1967, The effects of allografts on thymic epithelial reticular cells on the tissues of neonatally thymectomized mice, Blood, 29:29.PubMedGoogle Scholar
  45. Hedge, G.A., 1976, Hypothalamic and pituitary effects of prostaglandins on ACTH secretion, Prostaglandins, 11:293.PubMedCrossRefGoogle Scholar
  46. Hooper, J.A., McDaniel, M.C., Thurman, G.B., Cohen, G.H., Schulof, R.S., and Goldstein, A.L., 1975, Purification and properties of bovine thymosin, Ann. N.Y. Acad. Sci., 249:125.PubMedCrossRefGoogle Scholar
  47. Hu, S-K., Low, T.L.K., and Goldstein, A.L, 1979, “in vivo” induction of terminal deoxynucleotidyl transferase (TdT) by thymosin in hydrocortisone acetate (HCA) treated mice, Proc. Fed. Am. Soc. Exp. Biol., 38:4501, abstract.Google Scholar
  48. Hu, S-K., Thurman, G.B., Low, T.L.K., McClure, J., and Goldstein, A. L., 1980, Multifaced role of purified thymosin peptides in differentiation and function of T cells, New Trends Immunol. Cancer Ther., in press.Google Scholar
  49. Hunt, L.T., and Dayhoff, M.D., 1977, Amino-terminal sequence identity of ubiquitin and the non histonic component of nuclear protein A24, Biochem. Biophys. Res. Commun., 74:650.Google Scholar
  50. Law, L.W., Goldstein, A.L. and White, A., 1968, Influence of thymosin on immunological competence of lymphoid cells from thymectomized mice, Nature, 219:1391.PubMedCrossRefGoogle Scholar
  51. Leuchars, E., Cross, A.M., and Dukov, P., 1965, The restoration of immunologic function by thymus grafting in thymectomized irradiated mice, Transplantation, 3:28.PubMedCrossRefGoogle Scholar
  52. Lintern-Moore, S., and Pantelouris, E.M., 1975, Ovarian development in athymic nude mice. The size and composition of the follicle population, Mech. Age. Dev., 4:385.CrossRefGoogle Scholar
  53. Lintern-Moore, S., and Pantelouris, E.M., 1976, Ovarian development in athymic nude mice. III. The effect of PMSG and oestradiol upon the size and composition of the ovarian follicle population, Mech. Age. Dev., 5:33.CrossRefGoogle Scholar
  54. Low, T.L.K., Thurman, G.B., McAdoo, M., McClure, J.E., Rossio, J.L., Naylor, P.H., and Goldstein, A.L., 1979, The chemistry and biology of thymosin, J. Biol. Chem., 254:981.PubMedGoogle Scholar
  55. Low, T.L.K. and Goldstein, A.L., 1979, The chemistry and biology of thymosin, J. Biol. Chem., 254:987.PubMedGoogle Scholar
  56. Low, T.L.K., Hu, S-K., and Goldstein, A.L., 1981, Complete amino acid sequence of bovine thymosin B4: A thymic hormone that induces a terminal deoxynucleotidyl transferase activity in thymocyte populations, Proc. Natl. Acad. Sci., 78:1166.Google Scholar
  57. Martin, C.R., 1964, Influence of thymectomy on growth of secondary reproductive structures in rats, Am. J. Physiol., 206:193.PubMedGoogle Scholar
  58. Martin, C.R., 1976, Textbook of Endocrine Physiology, Williams and Wilkins, Baltimore, p. 390.Google Scholar
  59. Michael, S.D., Taguchi, O. and Nishijuka, Y., 1981, Changes in hypophyseal hormones associated with accelerated aging and tumorigenesis of the ovaries in neonatally thymectomized mice, Endocrinology, 108:2375.PubMedCrossRefGoogle Scholar
  60. Miller, J.F.A.P., 1966, The thymus in relation to the development of immunological capacity, in: “Experimental and clinical studies,” G.E.W. Wolstenholme and R. Porter, eds., Ciba Found. Symp., Churchill, London, p. 153.Google Scholar
  61. Miller, L., and Martin, C.R., 1969, Further investigation of thymic influence on reproductive structure maturation, Proc. Fed. Amer. Soc. Exp. Biol., 28:774, abstract.Google Scholar
  62. Monjan, A.A., 1981, Stress and immunologic competence; studies in animals, in: “Psychoneuroimmunology,” R. Ader, ed., in press.Google Scholar
  63. Nishizuka, Y. and Sakakura, T., 1971, Ovarian dysgenesis induced by neonatal thymectomy in the mouse, Endocrinology, 89:886.Google Scholar
  64. Pasmino, N.H., Ihle, J.N. and Goldstein, A.L., 1978, Induction “in vivo” and “in vitro” of terminal deoxynucleotidyl transferase by thymosin in bone marrow cells from athymic mice, J. Exp. Med., 147:708.CrossRefGoogle Scholar
  65. Pierpaoli, W., and Besedovsky, H.O., 1975, Role of the thymus in programming of neuroendocrine functions, Clin. Exp. Immunol., 20:323.PubMedGoogle Scholar
  66. Pierpaoli, W., and Maestroni, G.J.M., 1977, Pharmacological control of the immune response by blockade of the early hormonal changes following antigen injection, Cell. Immunol., 31:355.PubMedCrossRefGoogle Scholar
  67. Pierpaoli, W., and Sorkin, E., 1972a, Hormones, thymus, and lymphocyte functions, Experientia, 28:1385.PubMedCrossRefGoogle Scholar
  68. Pierpaoli, W., and Sorkin, E., 1972b, Alterations of adrenal cortex and thyroid in mice with congenital absence of the thymus, Nature, New Biol., 238:282.CrossRefGoogle Scholar
  69. Pierpaoli, W., Fabris, N., and Sorkin, E., 1970, Developmental hormones and immunological maturation, in: “Hormones and the immune response,” G.E.W. Wolstenholme and J. Knight, eds., Ciba Found. Study Group No. 36, Churchill, London, p. 126.Google Scholar
  70. Pierpaoli, W., Kopp, H.G., and Bianchi, E., 1976, Interdependence of thymic and neuroendocrine functions in ontogeny, Clin. Exp. Immunol., 24:501.PubMedGoogle Scholar
  71. Rosoff, B., and Martin, C.R., 1971, The influence of thymectomy and sham operation on prostate gland responses of hooded rats to gonadotrophins, Gen. Comp. Endocr., 16:484.PubMedCrossRefGoogle Scholar
  72. Saxena, R.K., and Talwar, G.P., 1977, An anterior pituitary factor stimulates thymidine incorporation in isolated thymocytes, Nature, 268:57.PubMedCrossRefGoogle Scholar
  73. Scheid, M.P., Hoffman, M.K., Komuro, K., Hammerling, H., Boyse, E.A., Cohen, G.H., Hooper, J.A., Schulof, R.S., and Goldstein A.L., 1973, Differentiation of T cells induced by preparations from thymus and by nonthymic agents, J. Exp. Med., 138:1027.PubMedCrossRefGoogle Scholar
  74. Scherrer, H., Seidah, N.G., Benjannet, S., Crine, P., Lis, M., and Chretien, M., 1978, Biosynthesis of a ubiquitin-related peptide in rat brain and in human and mouse pituitary tumors, Biochem. Biophys. Res. Commun., 84:874.PubMedCrossRefGoogle Scholar
  75. Seidah, N.G., Crine, P., Benjannet, S., Scherrer, H., and Chretien, M., 1978, Isolation and partial characterization of a biosynthetic N-terminal metionyl peptide of bovine pars intermedia: Relationship to ubiquitin, Biochem. Biophys. Res. Commun., 80:600.PubMedCrossRefGoogle Scholar
  76. Stadecker, M.J., and Unanue, E.R., 1979, Macrophage secretion of micromolecules, Ann. N.Y. Acad. Sci., 332:550.PubMedCrossRefGoogle Scholar
  77. Straus, E., Muller, J.E., Choi, H-S., Paronetto, F., and Yalow, R.S., 1977, Immunohistochemical localization in rabbit brain of a peptide resembling the COOH-terminal octapeptide of cholecystokinin, Proc. Natl. Acad. Sci., 74:3033.PubMedCrossRefGoogle Scholar
  78. Strausser, H.R., Bober, L.A., Bisci, R.A. Schillcock, J.A., and Goldstein, A.L., 1971, Stimulation of the hemagglutinin response of aged mice by cell-free lymphoid tissue fractions and bacteria endotoxin, Exp. Gerontol., 6:373.PubMedCrossRefGoogle Scholar
  79. Talal, N., Dauphinée, M., Philarisetty, R., and Goldblum, R., 1975, Effect of thymosin on thymocyte proliferation and autoimmunity in NZB mice, Ann. N.Y. Acad. Sci., 249:438.PubMedCrossRefGoogle Scholar
  80. Thurman, G.B., Rossio, J.L., and Goldstein, A.L., 1977, Antibody-forming cells with specificity for syngeneic and allogeneic (Thymocyte) tissue antigens following lipopolysaccharide mitogenic stimulation, Transplant. Proc., 9:1201.Google Scholar
  81. Trainin, N., Small, M., Ziport, D., Umiel, T., Kook, A.I. and Rotter, V., 1975, in: “The Biological activity of thymic hormones,” D.W. VanBekkum, ed., Kooyker Scientific. Pub., Amsterdam, p.261.Google Scholar
  82. Weinstein, Y., 1978, Impairment of the hypothalamo-pituitary-ovarian axis of the athymic nude mouse, Mech. Age. Dev., 8:63.CrossRefGoogle Scholar
  83. Wetzel, R., Heyneker, H.L., Goeddel, D.V., Jhurani, P., Shapiro, J., Crea, R., Low, T.L.K., McClure, J.E., and Goldstein, A.L., 1980, Production of biologically active Nα desacetylthymosin α 1 in Escherichia coli through expression of a chemically synthesized gene, Biochemistry, 19:6096.PubMedCrossRefGoogle Scholar
  84. Wilkinson, K.D., Uran, M.K., and Haos, A.L., 1980, Ubiquitin is the ATP-dependent proteolysis Factor I of rabbit reticulocytes, J. Biol. Chem., 255:7529.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Nicholas R. Hall
    • 1
  • Allan L. Goldstein
    • 1
  1. 1.Dept. of BiochemistryThe George Washington University, School of Medicine and Health SciencesUSA

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