Recent Advances in Thymic Hormone Research

  • Marcelo B. Sztein
  • Allan L. Goldstein
Part of the NATO ASI Series book series (NSSA, volume 120)


The essential role of the thymus gland in the development of a competent immune system was established by experiments in which it was found that the surgical removal of the thymus within 24 hours after birth, resulted in a dramatic impairment of the immune function (1,2). Neonatal thymectomy was also accompanied by a high incidence of early death due primarily to overwhelming infections. Additionally, recent evidence suggests that the thymus gland might be critical not only in mediating lymphocyte maturation and differentiation, but also in maintaining a normal immune balance by modulating normal immune response (3–12).


Migration Inhibition Factor Acquire Immune Deficiency Syndrome Thymic Epithelial Cell Primary Immunodeficiency Disease Human Peripheral Blood Lymphocyte 
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  1. 1.
    O. Archer, and J. C. Pierce, Role of thymus in development of the immune response, Fed. Proc. 20:26 (1961).Google Scholar
  2. 2.
    J. F. A. P. Miller, Immunological functions of the thymus, The Lancet 2: 748 (1961).CrossRefGoogle Scholar
  3. 3.
    M. B. Sztein, and A. L. Goldstein, Thymic Hormones - A Clinical Update, Springer Seminar Immunopathol. in press (1985).Google Scholar
  4. 4.
    R. S. Schulof, and A. L. Goldstein, Clinical applications of thymosin and other thymic hormones, in: “Recent Advances in Clinical Immunology”, R. A. Thompson, and N. R. Rose, ed., Churchill Livingstone, New York, p. 243 (1983).Google Scholar
  5. 5.
    R. Schulof, P. H. Naylor, M. M. Zatz, and A. L. Goldstein, Thymic physiology and biochemistry, in: “Molecular and physiological basis of systemic function”, H. E. Spiegel, ed., Academic Press, New York, in press (1985).Google Scholar
  6. 6.
    M. B. Sztein, S. A. Serrate, and A. L. Goldstein, Modulation of interleukin 2 receptor expression in human lymphocytes by thymic hormones, submitted for publication.Google Scholar
  7. 7.
    M. M. Zatz, J. Oliver, C. Samuels, A. B. Skotnicki, M. B. Sztein, and A. L. Goldstein, Thymosin increases production of T-cell growth factor by normal peripheral blood lymphocytes, Proc. Nat. Acad. Sci. USA 81: 2882 (1984).CrossRefGoogle Scholar
  8. 8.
    M. M. Zatz, A. B. Skotnicki, J. M. Bailey, J. Oliver, and A. L. Goldstein, Mechanisms of action of Thymosin. H. Effects of aspirin and thymosin on enhancement of IL-2 production, Immunopharmac. 9: 189 (1985).Google Scholar
  9. 9.
    M. M. Zatz, and A. L. Goldstein, Mechanisms of action of Thymosin: I. Thymosin Fraction 5 increases lymphokine production by mature murine T cells responding in a mixed lymphocyte reaction, J. Immunol. 134: 1032 (1985).PubMedGoogle Scholar
  10. 10.
    J. E. Taldmadge, K. A. Uithoven, B. F. Lenz, and M. A. Chirigos, Immunomodulation and therapeutic characterization of thymosin fraction 5, Cancer Immunol. Immunother. 18:185 (1984).Google Scholar
  11. 11.
    T. Umiel, M. Pecht, and N. Trainin, THF, a thymic hormone, promotes interleukin-2 production in intact and thymus-deprived mice, J. Biol. Resp. Mod. 3: 423 (1984).Google Scholar
  12. 12.
    J. Shoham, and I. Eshel, Thymic hormonal activity on human peripheral blood lymphocytes, in vitro. IV. Proliferative response to allogeneic tumor cells in healthy adults and cancer patients, Int. J. Immunopharmac. 5: 515 (1983).CrossRefGoogle Scholar
  13. 13.
    B. F. Haynes, The human thymic microenvironment, Adv. Immunol. 36: 87 (1984).PubMedCrossRefGoogle Scholar
  14. 14.
    R. S. Schulof, Thymic peptide hormones: Basic properties and clinical applications in cancer, in: “CRC Critical Reviews in Oncology/ Hematology”, S. Davis, ed., CRC Press, Boca Raton, Vol. 3, p. 309 (1985).Google Scholar
  15. 15.
    T. L. K. Low, and A. L. Goldstein, Thymosin, peptidic moieties and related agents, in: “Immune modulation agents and their mechanisms”, R. L. Fenickel and M. A. Chirigos, eds., Marcel Decker Inc., New York, p. 135 (1984).Google Scholar
  16. 16.
    M. M. Zatz, T. L. K. Low, and A. L. Goldstein, Role of Thymosin and other thymic hormones in T-cell differentiation, in: “Biological responses in cancer”, E. Mihick, ed., Plenum Press, New York, Vol. 1, p. 219 (1982).Google Scholar
  17. 17.
    A. L. Goldstein, T. L. K. Low, G. B. Thurman, M. M. Zatz, N. R. Hall, J. E. McClure, S. Hu, and R. S. Schulof, Thymosin and other hormone-like factors of the thymus gland, in: “Immunological approaches to cancer therapeutics”, E. Mihick, ed. J. Wiley and Sons, New York, p. 137 (1982).Google Scholar
  18. 18.
    H. R. Higley, and G. Rowden, Immunocytochemical localization of Thymosin and Thymopoietin in human, rat and murine thymus, in: “Thymic Hormones and Lymphokines”, A. L. Goldstein, ed., Plenum Press, New York, p. 135 (1984).Google Scholar
  19. 19.
    P. H. Naylor, J. E. McClure, B. L. Spangelo, T. L. K. Low, and A. L. Goldstein, Immunochemical studies in thymosin: Radioimmunoassay of thymosin beta 4, Immunopharmac. 7: 9 (1984).Google Scholar
  20. 20.
    K. Ogha, G. F. Incefy, K. F. Folk, B. W. Erickson, and R. A. Good, Radioimmunoassay for the thymic hormone serum thymic factor (FTS), J. Immunol. Methods 57:171 (1983).Google Scholar
  21. 21.
    P. J. Lisi, J. W. Teipel, G. Goldstein, and M. Schiffman, Improved radioimmunoassay technique for measuring serum thymopoietin, Clinica Chimica Acta 107: 111 (1980).Google Scholar
  22. 22.
    N. R. Hall, and A. L. Goldstein, Endocrine regulation of host immunity. The role of steroids and thymosin, in: “Immune modulation agents and their mechanisms”, R. L. Fenickel and M. A Chirigos, eds., Marcel Decker Inc., New York, p. 533 (1984).Google Scholar
  23. 23.
    A. A. Haritos, O. Tsolas, and B. L. Horecker, Distribution of prothymosin in rat tissues, Proc. Nat. Acad. Sci. USA 81: 1391 (1984)CrossRefGoogle Scholar
  24. 24.
    B. L. Horecker, Thymosin beta 4. Distribution and biosynthesis in invertebrate cells and tissues, in: “Thymic Hormones and Lymphokines”, A. L. Goldstein, ed., Plenum Press, New York, p. 77 (1984).Google Scholar
  25. 25.
    N. R. Hall, J. P. McGillis, B. L. Spangelo, and A. L. Goldstein, Evidence that thymosin and other biological response modifiers can function aâ neuroactive immunotransmitters, J. Immunol. 135: 806s (1985).Google Scholar
  26. 26.
    J. F. Bach, and M. Dardenne, Clinical aspects of thymulin (FTS), in: “Thymic Hormones and Lymphokines”, A. L. Goldstein, ed., Plenum Press, New York, p. 593 (1984).Google Scholar
  27. 27.
    A. B. Skotnicki, B. K. Dabrowska-Bernstein, M. P. Dabroski, A. J. Gorsky, J. Czarnecki, and J. Aleksandrowicz, Biological properties and clinical use of calf thymus extracts TFX-Polfa, in: “Thymic Hormones and Lymphokines”, A. L. Goldstein, ed., Plenum Press, New York, p. 545 (1984).Google Scholar
  28. 28.
    Stutman, Role of thymic hormones in T-cell differentiation, in: “Clinics in Immunology and Allergy”, J. F. Bach, guest ed., W. B. Saunders, Philadelphia, Vol. 3, p. 9 (1983).Google Scholar
  29. 29.
    W. W. Nowinsky, Fortgesetzte Beitrage zur Funktion des Thymus. Die Wirkungen des Thymocresins auf das Wachstum, Biochem. Z. 226: 415 (1930).Google Scholar
  30. A. L. Goldstein, F. D. Slatter, and A. White, Preparation, assay and partial purification of a thymic lymphocytopoietic factor (thymosin), Proc. Nat. Acad. Sci. USA 56:1010 (1966).Google Scholar
  31. 31.
    J. A. Hooper, M. C. McDaniel, G. B. Thurman, G. H. Cohen, R. S. Schulof, and A. L. Goldstein, The purification and properties of bovine thymosin, Ann. N. Y. Acad. Sci. 249: 125 (1975).PubMedCrossRefGoogle Scholar
  32. 32.
    R. Falchetti,G. Bergrsi, A. Eshkol, C. Cafiero, L. Adorini and L. Caprino, Pharmacological and biological properties of a calf thymus extract (TP1), Drugs Exptl. Clin. Res. 3:39 (1977).Google Scholar
  33. 33.
    A. B. Skotnicki, Biologiczna okthwnosc i wlasciwosci fizykochemiczne wyciagu grasiczego TFX, Pol. Tyg. Lek. 28: 1119 (1978).Google Scholar
  34. 34.
    A. L. Goldstein, T. L. K. Low, M. McAdoo, J. McClure, G. B. Thurman, J. L. Rossio, C. Y. Lai, D. Chang, S. S. Wang, C. Harvey, A. H. Ramel, and J. Meienhofer, Thymosin alpha 1: isolation and sequence analysis of an immunologically active thymic polypeptide Proc. Natl. Acad. Sci. USA 74:725 (1977).Google Scholar
  35. 35.
    G. Goldstein, Isolation of bovine thymin: A polypeptide hormone of the thymus, Nature 246: 11 (1974).Google Scholar
  36. 36.
    M. Dardenne, J. M. Pleau, N. K. Man, and J. F. Bach, Structural study of circulating thymic factor, a peptide isolated from pig serum. I. Isolation and purification, J. Biol. Chem. 252: 8040 (1977).Google Scholar
  37. 37.
    E. Bricas, T. Martinez, D. Blanot, G. Auger, M. Dardenne, J. M. Pleau, and J. F. Bach, The serum thymic factor and its synthesis, in: “Proceedings of the fifth international peptide symposium”, M. Goodman and J. Meienhofer, eds., John Wiley and Sons, New York, p. 564 (1982).Google Scholar
  38. 38.
    S. S. Wang, I. D. Kulesha, and D. P. Winter, Synthesis of thymosin alpha 1, J. Amer. Chem. Soc. 101:253 (1979).Google Scholar
  39. 39.
    R. Wetzel, H. L. Heinecker, D. V. Goeddel, P. Jhurani, J. Shapiro, R. Crea, T. L. K. Low, J. E. McClure, G. B. Thurman, and A. L. Goldstein, Production of biologically active N-desacetyl thymosin alpha 1 in Escherichia coli through expression of a chemically synthetized gene, Biochemistry 19: 6096 (1980).Google Scholar
  40. 40.
    A. Ahmed, D. M. Wong, G. B. Thurman, T. L. K. Low, A. L. Goldstein, S. J. Sharkis, and I. Goldschneider, T Lymphocyte maturation: cell surface markers and immune function induced by T lymphocyte cell-free product and by thymosin polypeptides, Ann. N. Y. Acad. Sci. 332: 81 (1979).CrossRefGoogle Scholar
  41. 41.
    J. Caldarella, G. J. Goodall, A. M. Felix, E. P. Heimer, S.B. Salvin, and B. L. Horecker, Thymosin alpha 11: a peptide related to thymosin alpha 1 isolated from calf thymosin fraction 5, Proc. Nat. Acad. Sci. USA 80:7424 (1983).Google Scholar
  42. 42.
    T. L. K. Low, and A. L. Goldstein, Chemical characterization of thymosin beta 4, J. Biol. Chem. 257:1000 (1982).Google Scholar
  43. 43.
    T. L. K. Low, S. S. Wang, and A. L. Goldstein, Solid phase synthesis of thymosin beta 4: Chemical and biological characterization of the synthetic peptide, Biochemistry 22: 733 (1983).Google Scholar
  44. 44.
    A. Wodnar-Filipowitz, U. Gubler, Y. Furuichi, M. Richardson, E. F. Nowoswiat, M. S. Poonian, and B. L. Horecker, Cloning and sequence analysis of cDNA for rat spleen thymosin beta 4, Proc. Nat. Acad. Sci. USA 81:2295 (1984).Google Scholar
  45. 45.
    R. W. Rebar, A. Miyake, T. L. K. Low, and A. L. Goldstein, Thymosin stimulates secretion of luteinizing hormone-releasing factor, Science 214: 669 (1981).Google Scholar
  46. 46.
    T. L. K. Low, and A. L. Goldstein, The chemistry and biology of thymosin. II. Aminoacid sequence analysis of thymosin alpha 1 and polypeptide beta 1, J. Biol. Chem. 254:987 (1979).Google Scholar
  47. 47.
    N. H. Pazmino, J. H. Ihle, R. N. McEwan, and A. L. Goldstein, Control of differentiation of thymosin precursors in the bone marrow by thymic hormones, Cancer Treat. Rep. 62:1749 (1978).Google Scholar
  48. 48.
    E. Hanapell, S. Davoust, and B. L. Horecker, Thymosin beta 8 and beta 9: Two new peptides isolated from calf thymus homologous to beta 4, Proc. Nat. Acad. Sci. USA 79:1708 (1982).Google Scholar
  49. 49.
    S. Erickson-Viitanen, S. Ruggieri, P. Natalini, and B. L. Horecker, Thymosin beta 10, a new analog of thymosin beta 4 in mammalian tissues, Arch. Biochem. Biophys. 225:407 (1983).Google Scholar
  50. 50.
    S. Erickson-Viitanen, and B. L. Horecker, Thymosin beta 11: a peptide from trout liver homologous to thymosin beta 4, Arch. Biochem. Biophys. 233:815 (1984).Google Scholar
  51. 51.
    A. A. Haritos, G. J. Goodall, and B. L. Horecker, Prothymosin alpha: Isolation and properties of the major immunoreactive form of thymosin alpha 1 in rat thymus, Proc. Nat. Acad. Sci. USA 81:1008 (1984).Google Scholar
  52. 52.
    A. A. Haritos, S. B. Salvin, R. Blacherr, S. Stein, and B. L. Horecker, Parathymosin alpha: a peptide from rat tissues with structural homology to prothymosin alpha, Proc. Nat. Acad. Sci. USA 82:1050 (1985).Google Scholar
  53. 53.
    D. H. Schlesinger, and G. Goldstein, The aminoacid sequence of thymopoietin II, Cell 5: 361 (1975).Google Scholar
  54. 54.
    M. Fujino, T. Fukada, S. Kawaji, S. S.inagawa, Y. Sugino, and M. of the nonatetracontapeptide corresponding proposed for thymopoietin II, Chem. Pharm. Bull. 25: 1496 (1977)Google Scholar
  55. 55.
    G. Goldstein, M.P. Scheid, E. A. Bois, D. H. Schlesinger, and J. Van Waunue, A synthetic pentapeptide with biological activity characteristic of the thymic hormone thymopoietin, Science 204: 1399 (1399)Google Scholar
  56. N. Trainin, A. Begerano, M. Strahilivitch, D. Goldring, N. Small, A thymic factor preventing wasting and influencing lymphopoiesis in mice, Israel J. Med. Sci. 2:549 (1966).Google Scholar
  57. Y. Yakir, and N. Trainin, Enrichment of in vitro and in vivo immunological activity of purified fractions of calf thymic hormone, J. Exp. Med. 148:71 (1978).Google Scholar
  58. 58.
    N. Trainin, V. Rotter, Y. Yakir, R. Leve, Z. Handzel, B. Shohat, and R. Zaizov, Biochemical and biological properties of THE in animal and human models, Ann. N. Y. Acad. Sci. 332: 9 (1979).PubMedCrossRefGoogle Scholar
  59. 59.
    G. Bernardi, and J. Comsa, Purification de l’hormone thymique par chromatographie sur colonne, Experientia 21: 416 (1965).Google Scholar
  60. 60.
    L. Kater, R. Oosteron, J. E. McClure, and A. L. Goldstein, Presence of thymosin in human thymic epithelium conditioned medium, Int. J. Immunopharmacol. 1: 273 (1979).PubMedCrossRefGoogle Scholar
  61. 61.
    A. Mizutani, A thymic hypocalcemic component, in: “Thymic hormones”, T. D. Luckey, ed., University Park Press, Baltimore, p. 193, (1973).Google Scholar
  62. 62.
    T. D. Luckey, W. G. Robey, and B. J. Campbell, LSH, a lymphocyte-stimulating hormone, in: “Thymic Hormones”, T. D. Luckey, ed., University Park Press, Baltimore, p. 167 (1973).Google Scholar
  63. 63.
    S. M. Milcu, I. Potop, R. Petersku, and E. Ghinea, Effect of thymosterin on lymphocytes in vitro, Endocrinology 14: 283 (1976).Google Scholar
  64. M. Dardenne, J. M. Pleau, B. Nabarra, P. Lefrancier, M. Derrien, M. Choay, and J. F. Bach, Contribution of Zn and other metals to the biological activity of the serum thymic factor, Proc. Nat. Acad. Sci. USA 79:5370 (1982).Google Scholar
  65. 65.
    A. L. Goldstein, T. L. K. Low, N. R. Hall, P. H. Naylor, and M. M. Zatz, Thymosin: can it retard aging by boosting immune capacity?, in: “Intervention in the aging process, part A: Quantitation, Epidemiology and Clinical Research”, W. Regelson and F. M. Sinex, eds., Alan R. Liss, Inc., New York, p. 169 (1984).Google Scholar
  66. N. H. Pazmino, J. N. Ihle, and A. L. Goldstein, Induction in vivo and in vitro of terminal deoxynucleotidyl transferase by thymosin in bone marrow cells from athymic mice, J. Exp. Med. 147:708 (1978).Google Scholar
  67. B. J. Mathieson, and B. J. Fowlkes, Cell surface antigen expression on thymocytes: Differentiation of intrathymic subsets, Immunol. Reviews 82:141 (1985).Google Scholar
  68. J. S. Levai, and V. Utermohlen, The effect of a human plasma thymic factor on human peripheral blood mononuclear cells subpopulations Clin. Immunol. Immunopathol. 27:433 (1983).Google Scholar
  69. 69.
    A. M. Kruisbeck, Summary of the results of the workshop, in: “The biological activity of the thymic hormones”, D. W. Van Bekkum, ed., Kooker Scientific Publications, Rotterdam, p. 209 (1975).Google Scholar
  70. 70.
    G. H. Cohen, J. A. Hooper, and A. L. Goldstein, Thymosin-induced differentiation of murine thymocytes in allogeneic mixed lymphocyte cultures, Ann. N.Y. Acad. Sci. 249: 145 (1975).PubMedCrossRefGoogle Scholar
  71. 71.
    L. A. Schafer, A. L. Goldstein, J. U. Gutterman, and E. M. Hersh, In vitro and in vivo studies with thymosin in cancer patients, Ann. N.Y. Acad. Sci. 277:609 (1976).Google Scholar
  72. 72.
    D. W. Wara, D. J. Barrett, A. J. Ammann, and M. J. Cowan, In vitro and in vivo enhancement of mixed lymphocyte culture reactivity by thymosin in patients with primary immunodeficiency disease, Ann. N. Y. Acad. Sci. 332:128 (1979).PubMedCrossRefGoogle Scholar
  73. 73.
    Shohan, and I. Eshel, Thymic hormonal effects on human peripheral blood lymphocytes in vitro. III. Conditions for mixed lymphocyte-tumor culture assay, J. Immunol. Methods 37: 261 (1980).CrossRefGoogle Scholar
  74. 74.
    M. Zatz, and A. L. Goldstein, Enhancement of murine thymocyte cytotoxic T cell responses by thymosin, Immunopharmacol. 6: 65 (1983).Google Scholar
  75. 75.
    Shoham, and M. Cohen, Thymic hormonal activity on human peripheral blood lymphocytes in vitro. V. Effect on induction of lymphocytotoxicity, Int. J. Immunopharmacol. 5: 523 (1983).CrossRefGoogle Scholar
  76. 76.
    Lau, and G. Goldstein, Functional effects of thymopoietin 32–36 (TP-5) on cytotoxic lymphocyte precursor units (CLP-U). I. Enhancement of splenic CLP-U in vitro and in vivo after suboptimal antigenic stimulation, J. Immunol. 124: 1861 (1980).Google Scholar
  77. 77.
    D. Frasca, M. Garavini, and G. Doria, Recovery of T-cell functions in aged mice injected with synthetic thymosin alpha 1, Cell Immunol. 72: 384 (1982).Google Scholar
  78. 78.
    W. B. Ershler, J. C. Herbert, A. J. Blow, S. R. Granter, and J. Lynch, Effect of thymosin alpha 1 on specific antibody response and susceptibility to infection in young and aged mice, Int. J. Immunopharmacol. in press (1985).Google Scholar
  79. W. B. Ershler, A. L. Moore, and M. A. Socinski, Influenza and aging: age-related changes and the effects of thymosin on the antibody response to influenza vaccine, J. Clin. Immunol. 4:445 (1984).Google Scholar
  80. M. J. Blankwater, L. A. Levert, A. C. W. Swart, and D. W. van Bekkum, Effect of various thymic and non-thymic factors on in vitro antibody formation by spleen cells from nude mice, Cell. Immunol. 35:242 (1978).Google Scholar
  81. D. D. F. Ma, A. H. Ho, and A. V. Hoffbrand, Effect of thymosin on glucocorticoid receptor activity and glucocorticoid sensitivity of human thymocytes, Clin. Exp. Immunol. 55:273 (1984).Google Scholar
  82. 82.
    G. D. Marshall, G. B. Thurman, J. L. Rossio, and A. L. Goldstein, In vivo generation of suppressor T cells by thymosin in congenically athymic nude mice, J. Immunol. 126:741 (1981).Google Scholar
  83. 83.
    G. D. Marshall, G. B. Thurman, and A. L. Goldstein, Regulation of in vitro generation of cell-mediated cytotoxicity. I. In vitro induction of suppressor T lymphocytes by thymosin, J. Reticuloendothel. Soc. 28:141 (1980).Google Scholar
  84. 84.
    J. J. Oppenheim, and S. Cohen, “Interleukine, Lymphokines and Cytokines”, Academic Press, San Francisco (1983).Google Scholar
  85. G. B. Thurman, C. Seals, T. L. K. Low, and A. L. Goldstein, Restorative effects of thymosin polypeptides on purified protein derivative-dependent migration inhibition factor production by the peripheral blood lymphocytes of adult thymectomized guinea pigs, J. Biol. Resp. Modif. 3:160 (1984).Google Scholar
  86. 86.
    J. Shoham, I. Eshel, M. Aboud, and S. Salzberg, Thymic hormonal activity on human peripheral blood lymphocytes in vitro. H. Enhancement of the production of immune interferon by activated T cells, J. Immunol. 125: 54 (1980).PubMedGoogle Scholar
  87. 87.
    D. Frasca, L. Adorini, and G. Doria, Production of and response to interleukin 2 in aging mice. Modulation by thymosin alpha 1, in: “Symposium on Lymphokines”, A. de Weck, ed., Interlaken, June 14–15 (1984).Google Scholar
  88. 88.
    K. A. Smith, Interleukin 2, Ann. Rev. Immunol. 2: 319 (1984).CrossRefGoogle Scholar
  89. M. M. Zatz, J. Oliver, M. B. Sztein, A. B. Skotnicki, and A. L. Goldstein, Comparison of the effects of thymosin and other thymic factors on modulation of interleukin-2 production, J. Biol. Resp. Modif. 4:365 (1985).Google Scholar
  90. 90.
    R. Ceredig, J. W. Lowenthal, M. Nabholtz,and R. M.cDonald, Expression of interleukin D receptors as a differentiation marker on intrathymic stem cells, Nature 314: 98 (1985).Google Scholar
  91. 91.
    D. H. Raulet, Expression and function of interleukin 2 receptors on immature thymocytes, Nature 314: 101 (1985).Google Scholar
  92. 92.
    T. Uchiyama, S. Broder, and T. A. Waldmann, A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac positive cells, J. Immunol. 126: 1393 (1981).PubMedGoogle Scholar
  93. 93.
    D. A. Cantrell, and K. A. Smith, Transient expression of interleukin 2 receptors. Consequences for T cell growth, J. Exp. Med. 158: 1895 (1983).PubMedCrossRefGoogle Scholar
  94. J. P. Flexman, P. G. Holt, G. Mayrhofer, B. I. Latham, and G. R. Shellam, The role of the thymus in the maintainance of natural killer cells in vivo, Cell. Immunol. 90:366 (1985).Google Scholar
  95. F. Bistoni, M. Baccarini, P. Puccetti, P. Marconi, and E. Garaci, Enhancement of natural killer cell activity in mice by treatment with a thymic factor, Cancer Immunol. Immunotherap. 17:51 (1984).Google Scholar
  96. 96.
    M. Fiorilli, M. C. Sirianni, V. Sorrentino, R. Testi, F. Aiuti, In vitro enhancement of bone marrow natural killer cells after incubation with thymopoietin 32–36 (TP-5), Thm_us 5:375 (1983).Google Scholar
  97. 97.
    M. C. Dokhelar, T. Tursz, M. Dardenne, and J. F. Bach, Effect of a synthetic thymic factor (Facteur Thymique Serique) on natural killer cell activity in humans, Int. J. Immunopharmacol. 5: 277 (1983).PubMedCrossRefGoogle Scholar
  98. 98.
    D. L. Healy, G. D. Hodgen, H. M. Shulte, G. P. Chrousos, D. L. Loriaux, N. R. Hall, and A. L. Goldstein, The thymus-adrenal connection: Thymosin has corticotropin-releasing activity in primates, Science 222: 1353 (1983).Google Scholar
  99. 99.
    M. I. Luster, G. A. Boorman, K. S. Korach, M. P. Dieter, and L. Hong, Mechanisms of estrogen-induced myelocytotoxicity: Evidence of thymic regulation, Int. J. Immunopharmacol. 6: 287 (1984).PubMedCrossRefGoogle Scholar
  100. L. S. Allen, J. E. McClure, A. L. Goldstein, M: S. Barkley, and S. D. Michael, Estrogen and thymic hormone interactions in the female mouse, J. Reproduct. Immunol. 6:25 (1984).Google Scholar
  101. 101.
    M. Dardenne, Evaluation of blood levels of thymic hormones in health and disease, in: “Thymic factor therapy”, N. A. Byrom, and J. R. Hobbs, eds., Serono Symposia Publications for Raven Press, New York, Vol. 16 (1984).Google Scholar
  102. 102.
    M. Dardenne, and J. F. Bach, Studies on the thymic products. I. Modification of rosette-forming cells by thymic extract determination of the target RFC subpopulation, Immunol. 25: 343 (1973).Google Scholar
  103. J. J. Twomey, G. Goldstein, V. M. Lewis, A. C. Bealmear, and R.A. Good, Bioassay determinations of thymopoietin and thymic hormone levels in human plasma, Proc. Nat. Acad. Sci. USA 74:2541 (1971).Google Scholar
  104. 104.
    J. E. McClure, N. Lameris, D. W. Wara, and A. L. Goldstein, Immunochemical studies on thymosin: Radioimmunoassay of thymosin alpha 1, J. Immunol. 128: 368 (1982).PubMedGoogle Scholar
  105. M. G. Mutchnick, D. F. Keren, F. E. Weller, J. E. McClure, and A. L. Goldstein, Measurement of thymosin alpha 1 by dissociation microELISA, J. Immunol. Methods 60:53 (1983).Google Scholar
  106. 106.
    P. H. Naylor, A. Friedman-Kien, E. Hersh, M. Erdos, and A. L. Goldstein, Thymosin alpha 1 and thymosin beta 4 in serum: Comparison of normal, cord, homosexual, and AIDS serum, Immunopharmacol. in press (1985).Google Scholar
  107. 107.
    J. P. McGillis, N. R. Hall, and A. L. Goldstein, Circadian rhythm of thymosin alpha 1 in normal and thymectomized mice, J. Immunol. 131: 148 (1983).Google Scholar
  108. J. M. Pleau, V. Fuentes, J L. Morgat, and J. F. Bach, Specific receptors for serum thymic factor (FTS) in lymphoblastoid cultured cell lines, Proc. Nat. Acad. Sci. USA 77:2861 (1980).Google Scholar
  109. 109.
    C. R. Garaci, M. R. Torrisi, T. Jessi, L. Frati, A. L. Goldstein, and E. Garaci, Receptors for thymosin alpha 1 on mouse thymocytes Cell Immunol. 91: 298 (1985).Google Scholar
  110. T. Audhya, M. A. Talle, and G. Goldstein, Thymopoietin radioreceptor assay utilizing lectin-purified glycoprotein from a biologically responsive T-cell line, Arch. Biochem. Biophys. 234:167 (1984).Google Scholar
  111. 111.
    R. S. Schulof, G. L. Simon, M. B. Sztein, C. R. Kessler, J. K. Courtless, J. M. Orenstein, P. D. Kind, S. Schlesselman, M. Robert-Guroff, P. H. Naylor, and A. L. Goldstein, Phase I/II trial of thymosin fraction 5 and thymosin alpha 1 in HTLV-III seropositive subjects, submitted for publication (1985).Google Scholar
  112. 112.
    P. H. Naylor, K. K. Oates, E. L. Cooper, P. Deschaux, L.F. Affronti, and A. L. Goldstein, Non-thymic sources of thymosin alpha 1, Proceedings of the 67th Endocrine Society Annual Meeting, June 19–21, Baltimore (1985).Google Scholar
  113. 113.
    J. Singh, The ultrastructure of epithelial reticular cells, in: The thymus gland“, M. F. Kendall, ed., Academic Press, London, p. 133 (1981).Google Scholar
  114. 114.
    B. F. Haynes, R. M. Scearce, D. F. Lobach, and L. L. Hensley, Phenotypic characterization and ontogeny of mesodermal-derived and endocrine epithelial components of the human thymic microenvironment, J. Exp. Med. 159: 1149 (1984).PubMedCrossRefGoogle Scholar
  115. 115.
    W. Savini, and M. Dardenne, Thymic hormone-containing cells. VI. Immunohistological evidence for the simultaneous presence of thymulin, thymopoietin and thymosin alpha 1 in normal and pathological human thymuses, Eur. J. Immunol. 14: 987 (1984).Google Scholar
  116. 116.
    W. Savino, P. C. Huang, A. Corrigan, S. Berrih, and M. Dardenne, Thymic hormone-containing cells. V. Immunohistological detection of metallothionein within the cells bearing thymulin (a zinc containing hormone) in human thymuses, J. Histochem. Cytochem. 32: 942 (1984).Google Scholar
  117. 117.
    M. C. Dalakas, R. Hubbard, G. Cunningham, B. Trapp, J. L. Sever, and A. L. Goldstein, Thymosin beta 4 is present in a subset of oligodendrocytes in the normal human brain, in: “Thymic hormones and lymphokines”, A. L. Goldstein, ed., Plenum Press, New York, p. 119 (1984).Google Scholar
  118. G. J. Goodall, J. I. Morgan, and B. L. Horecker, Thymosin beta 4 in cultured mammalian cell lines, Arch. Biochem. Biophys. 221:598 (1983).Google Scholar
  119. 119.
    C. H. Kirkpatrick, A. Khan, J. E. McClure, and A. L. Goldstein, Thymosin alpha 1-like material in dialysates of leukocyte extracts, in: “Immunobiology of Transfer Factor”, Academic Press, New York, p. 413 (1983).Google Scholar
  120. M. M. Zatz, J. E. McClure, and A. L. Goldstein, Immunoreactive thymosin alpha 1 is associated with murine T-cell lymphomas, Leukem. Res. 8:1003 (1984).Google Scholar
  121. 121.
    M. C. Dalakas, D. L. Madden, A. Krezlewiccz, J. L. Sever, and A.L. Goldstein, Human peripheral blood lymphocytes bear markers for thymosins (alpha 1, alpha 7, beta 4), in: “Thymic hormones and lymphokines”, A. L. Goldstein, ed., Plenum Press, New York, p. 111 (1984).Google Scholar
  122. 122.
    A. L. Goldstein, and R. S. Schulof, Thymosins in the treatment of cancer, in: “Immunity to cancer”, A. Reif, and M. Mitchell, eds. in press (1985).Google Scholar
  123. 123.
    D. W. Wara, M. J. Cowan, A. J. Ammann, Thymosin fraction 5 therapy in patients with primary immunodeficiency disorders, in: “Thymic Factor Therapy”, N. A. Byrom, and J. R. Hobbs, eds., Serono Symposia Publications for Raven Press, New York, Vol. 16, p. 123 (1984).Google Scholar
  124. 124.
    F. Aiuti, and L. Businco, Effects of thymic hormones in Immunodeficiency, in: “Clinics in Immunology and Allergy”, J. F. Bach, guest ed., Saunders Co., Philadelphia, Vol. 3, p. 187 (1983).Google Scholar
  125. 125.
    Z. T. Handzel, Z. Dolfin, S. Levin, Y. Altman, T. Hahn, N. Trainin, and N. Gadot, EffecS of thymic humoral factor on cellular immune functions of normal children and of pediatric patients with Ataxia-Telangiectasia and Down’s syndrome, Pediatrics Res. 13: 803 (1979).Google Scholar
  126. 126.
    J. D. Stinnett, L. D. Loose, P. Miskell, C. L. Tenney, S. J. Gonce, and J. W. Alexander, Synthetic immunomodulators for prevention of fatal infections in a burned guinea pig model, Ann. Sur. 198: 53 (1983).Google Scholar
  127. T. Abiko, and H. Sekino, Deacetyl-thymosin beta 4: Synthesis and effect on the impaired peripheral T-cell subsets in patients with chronic renal failure, Chem. Pharm. Bull. 32:4497 (1984).Google Scholar
  128. A. S. Fauci, A. M. Macher, D. L. Longo, H. C. Lane, A. H. Rook, H. Masur, and E. P. Gelmann, Acquired immunodeficiency syndrome: Epidemiologic, clinical, immunological and therapeutic considerations, Ann. Int. Med. 100:92 (1984).Google Scholar
  129. 129.
    E. M. Hersh, P. W. A. Mansell, J. M. Reuben, A. Rios, and G.R. Newel, Immunological characterization of patients with acquired immune deficiency syndrome-related symptom complex, and a related life-style, Cancer Res. 44: 5894 (1984).Google Scholar
  130. J. M. Dwayer, J. G. McNamara, L. H. Sigel, and C. C. Wood, Immunological abnormalities in patients with the acquired immune deficiency syndrome (AIDS) - A review, Clin. Immunol. Rev. 3:25 (1984).Google Scholar
  131. 131.
    P. H. Naylor, R. S. Schulof, M. B. Sztein, T. J. Spira, P. R. McCurdy, F. Darr, C. M. Kessler, G. Simon, and A. L. Goldstein, Thymosin in the early diagnosis and treatment of high risk homosexuals and hemophiliacs with AIDS-like immune dysfunction, Ann. N.Y. Acad. Sci. 437: 88 (1984).PubMedCrossRefGoogle Scholar
  132. 132.
    J. L. Murray, J. M. Reuben, C. G. Munn, G. Newell, P. W. A. Mansell, and E. M. Hersh, In vitro modulation of purine enzyme metabolism and lympho.:yte marker expression by thymosin fraction 5 in homosexual males, Int. J. Immunopharmacol. 7:661 (1985).Google Scholar
  133. F. M. Collins, and N. E. Morrison, Restoration of T-cell responsiveness by thymosin: Expression of anti-tuberculous immunity in mouse lungs, Infect. Immun. 23:330 (1979).Google Scholar
  134. 134.
    S. B. Salvin, and R. Neta, Resistance and susceptibility to infection in inbred murine strains. I. Variations in the response to thymic hormones in mice infected with Candida albicans, Cell Immunol. 75: 160 (1983).Google Scholar
  135. R. Nets, and S. B. Salvin, Resistance and susceptibility to infections in inbred murine strains. H. Variations in the effect of treatment with thymosin fraction 5 on the release of lymphokines in vivo, Cell. Immunol. 75:173 (1983).Google Scholar
  136. F. Aiuti, M. C. Sirianni, M. Fiorilli, R. Paganelli, A. Stella, and G. Turbessi, A placebo-controlled trial of thymic hormone treatment of recurrent herpes simplex labialis infection in immunodeficient host: Results after 1-year follow-up, Clin. Immunol. Immunopathol. 30:11 (1984).Google Scholar
  137. M. Demartino, M. E. Rossi, A. T. Muccioli, and A. Vierucci, T lymphocytes in children with respiratory infections: Effect of the use of thymostimulin on the alterations of T-cell subsets, Int. J. Tiss. Reac. VI:223 (1984).Google Scholar
  138. 138.
    M. E. Gershwin, A. Ahmed, A. D. Steinberg, G. B. Thurman, and A.L. Goldstein, Correction of T cell function by thymosin in New Zealand mice, J. Immunol. 113: 1068 (1974).PubMedGoogle Scholar
  139. N. Talai, M. Dauphinee, R. Pillarisetty, and R. Goldblum, Effects of thymosin on thymocyte proliferation and autoimmunity in NZB mice, Ann. N.Y. Acad. Sci. 249:438 (1975).Google Scholar
  140. V. Tomazik, C. M. Suter, and P. B. Chretien, Experimental autoimmune thyroiditis: Modulation of the disease in high and low responser mice by thymosin, Clin. Exp. Immunol. 58:83 (1984).Google Scholar
  141. 141.
    J. Woyciechowska, A. L. Goldstein, and B. Driscoll, Experimental allergic encephalomyelitis in guinea pigs. Influence of thymosin fraction 5 in the disease, J. Neuroimmunol. 7: 215 (1985).PubMedCrossRefGoogle Scholar
  142. 142.
    S. D. Horowitz, W. Borcherding, A. Vishnu Moorthy, R. Chesney, H. Schulte-Wisserman, and R. Hong, Induction of suppressor T cells in systemic lupus erythematosus by thymosin and cultured thymic epithelium, Science 197: 999 (1977).Google Scholar
  143. 143.
    E. M. Veys, H. Mielants, G. Verbruggen, T. Spiro, E. Nedweck, D. Power, and G. Goldstein, Thymopoietin pentapeptide (thymopentin, TP5) in the treatment of rheumatoid arthritis. A compilation of several short and long-term clinical studies, J. Rheumatol. 11: 462 (1984).Google Scholar
  144. 144.
    M. A. Chirigos, In vivo and in vitro studies with thymosin, in: “Control of neoplasia by modulation of the immune system”, M.A. Chirigos, ed., Raven Press, New York, p. 241 (1977).Google Scholar
  145. 145.
    Y. Umeda, A. Sakamoto, J. Nakamura, H. Ishitsuka, and Y. Yagi, Thymosin alpha 1 restores NK cell activity and prevents tumor progression in mice immunosuppressed by cytostatics or X-rays, Cancer Immunol. Immunother. 15:78 (1983).Google Scholar
  146. 146.
    Y. Ohta, E. Tezuka, S. Tamura, and Y. Yagi, Protection of 5-fluorouracil induced bone marrow toxicity by thymosin alpha 1, Int. J. Immunopharmac. in press (1985).Google Scholar
  147. 147.
    N. Takeichi, Y. Koga, T. Fujii, and H. Kobayashi, Restoration of T cell function and induction of anti-tumor immune response in T-cell depressed spontaneously hypertensive rats by treatment with thymosin fraction 5, Cancer Res. 45: 487 (1985).Google Scholar
  148. 148.
    M. H. Cohen, P. B. Chretien, B. C. Ihed, B. E. Fossieck, R. Makuch, P. A. B.nn, A. V. Johnston, S. E. Shackney, M. J. Matthews, S. D. Lipson, D. E. Kenady, and J. D. Minna, Thymosin fraction 5 and intensive combination chemotherapy. Prolonging the survival of patients with small cell lung cancer, JAMA 241: 1813 (1979).Google Scholar
  149. 149.
    E. Azizi, H. J. Brenner, and J. Shoham, Postsurgical adjuvant treatment of malignant melanoma patients by the thymic factor thymostimulin, Drug Res. 9: 1043 (1984).Google Scholar
  150. 150.
    R. S. Schulof, M. J. Lloyd, P. A. Cleary, S. R. Palaszinski, D.A. Mai, J. W. Cox, O. Alabaster, and A. L. Goldstein, A randomized trial to evaluate the immunorestorative properties of synthetic thymosin alpha 1 in patients with lung cancer, J. Biol. Resp. Mod. 4:147 (1985).Google Scholar
  151. 151.
    A. L. Goldstein, The history of the development of thymosin: Chemistry, biology and clinical applications, in: “Transactions of the American Clinical and Climatological Association”, 89th Annual Meeting, Ponte Vedra, Florida, October 25–27 (1976), Waverly Press, Inc., p. 79 (1977).Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Marcelo B. Sztein
    • 1
  • Allan L. Goldstein
    • 1
  1. 1.Departments of Medicine and BiochemistryThe George Washington University School of MedicineUSA

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