Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Aug;83(16):6107–6111. doi: 10.1073/pnas.83.16.6107

Modulation of interleukin 2 receptor expression on normal human lymphocytes by thymic hormones.

M B Sztein, S A Serrate, A L Goldstein
PMCID: PMC386448  PMID: 3090550

Abstract

The expression of interleukin 2 receptors (IL-2R) is a critical step leading to normal lymphocyte proliferation. Since thymosin fraction 5 (TF5), a thymic hormone preparation, enhances lymphoproliferative responses of human cells, we examined the effects of TF5 on the expression of IL-2R on mitogen-stimulated human lymphocytes. TF5 significantly increased the percentage and antigen density of cells expressing IL-2R after stimulation with an optimal concentration of phytohemagglutinin (PHA) when the cells from the same donor exhibited suboptimal responses to PHA alone. The same effect was observed with a suboptimal PHA concentration and with OKT3 monoclonal antibody stimulation. Thymosin alpha 1, a synthetic polypeptide originally isolated in its native form from TF5, was also able to increase IL-2R expression in response to PHA, suggesting that it is the active species in TF5. The enhancement of IL-2R expression was paralleled by increased proliferative responses. Increased IL-2R expression appears to be the direct effect of thymic hormones, since abrogation of interleukin 2 production by cyclosporin A did not affect TF5-mediated enhancement of PHA-induced IL-2R expression. These results point to a physiological role of thymic hormones in the maintenance of normal levels of IL-2R expression. This immunoregulatory activity of thymic hormones might be relevant in the treatment of conditions where there is decreased IL-2R expression, such as the acquired immune-deficiency syndrome, or in the restoration of normal IL-2R expression to lymphocytes from aged individuals.

Full text

PDF
6107

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baxevanis C. N., Perez S., Kokkinopoulos D., Papamichail M. The biological effect of three thymosin fraction 5 polypeptides in the murine mixed lymphocyte reaction. Immunology. 1985 Apr;54(4):723–730. [PMC free article] [PubMed] [Google Scholar]
  2. Cantrell D. A., Smith K. A. Transient expression of interleukin 2 receptors. Consequences for T cell growth. J Exp Med. 1983 Dec 1;158(6):1895–1911. doi: 10.1084/jem.158.6.1895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Depper J. M., Leonard W. J., Drogula C., Krönke M., Waldmann T. A., Greene W. C. Interleukin 2 (IL-2) augments transcription of the IL-2 receptor gene. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4230–4234. doi: 10.1073/pnas.82.12.4230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Elliott J. F., Lin Y., Mizel S. B., Bleackley R. C., Harnish D. G., Paetkau V. Induction of interleukin 2 messenger RNA inhibited by cyclosporin A. Science. 1984 Dec 21;226(4681):1439–1441. doi: 10.1126/science.6334364. [DOI] [PubMed] [Google Scholar]
  5. Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
  6. Hooper J. A., McDaniel M. C., Thurman G. B., Cohen G. H., Schulof R. S., Goldstein A. L. Purification and properties of bovine thymosin. Ann N Y Acad Sci. 1975 Feb 28;249:125–144. doi: 10.1111/j.1749-6632.1975.tb29063.x. [DOI] [PubMed] [Google Scholar]
  7. Huang K. Y., Kind P. D., Jagoda E. M., Goldstein A. L. Thymosin treatment modulates production of interferon. J Interferon Res. 1981;1(3):411–420. doi: 10.1089/jir.1981.1.411. [DOI] [PubMed] [Google Scholar]
  8. Katzen D., Chu E., Terhost C., Leung D. Y., Gesner M., Miller R. A., Geha R. S. Mechanisms of human T cell response to mitogens: IL 2 induces IL 2 receptor expression and proliferation but not IL 2 synthesis in PHA-stimulated T cells. J Immunol. 1985 Sep;135(3):1840–1845. [PubMed] [Google Scholar]
  9. Kaye J., Gillis S., Mizel S. B., Shevach E. M., Malek T. R., Dinarello C. A., Lachman L. B., Janeway C. A., Jr Growth of a cloned helper T cell line induced by a monoclonal antibody specific for the antigen receptor: interleukin 1 is required for the expression of receptors for interleukin 2. J Immunol. 1984 Sep;133(3):1339–1345. [PubMed] [Google Scholar]
  10. Kermani-Arab V., Salehmoghaddam S., Danovitch G., Hirji K., Rezai A. Mediation of the antiproliferative effect of cyclosporine on human lymphocytes by blockade of interleukin 2 biosynthesis. Transplantation. 1985 Apr;39(4):439–442. doi: 10.1097/00007890-198504000-00019. [DOI] [PubMed] [Google Scholar]
  11. Krönke M., Leonard W. J., Depper J. M., Arya S. K., Wong-Staal F., Gallo R. C., Waldmann T. A., Greene W. C. Cyclosporin A inhibits T-cell growth factor gene expression at the level of mRNA transcription. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5214–5218. doi: 10.1073/pnas.81.16.5214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lipkowitz S., Greene W. C., Rubin A. L., Novogrodsky A., Stenzel K. H. Expression of receptors for interleukin 2: Role in the commitment of T lymphocytes to proliferate. J Immunol. 1984 Jan;132(1):31–37. [PubMed] [Google Scholar]
  13. Makinodan T., James S. J., Inamizu T., Chang M. P. Immunologic basis for susceptibility to infection in the aged. Gerontology. 1984;30(5):279–289. doi: 10.1159/000212647. [DOI] [PubMed] [Google Scholar]
  14. Malek T. R., Chan C., Glimcher L. H., Germain R. N., Shevach E. M. Influence of accessory cell and T cell surface antigens on mitogen-induced IL 2 receptor expression. J Immunol. 1985 Sep;135(3):1826–1833. [PubMed] [Google Scholar]
  15. Meltzer M. S., Oppenheim J. J. Bidirectional amplification of macrophage-lymphocyte interactions: enhanced lymphocyte activation factor production by activated adherent mouse peritoneal cells. J Immunol. 1977 Jan;118(1):77–82. [PubMed] [Google Scholar]
  16. Meuer S. C., Hussey R. E., Cantrell D. A., Hodgdon J. C., Schlossman S. F., Smith K. A., Reinherz E. L. Triggering of the T3-Ti antigen-receptor complex results in clonal T-cell proliferation through an interleukin 2-dependent autocrine pathway. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1509–1513. doi: 10.1073/pnas.81.5.1509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Prince H. E., Kermani-Arab V., Fahey J. L. Depressed interleukin 2 receptor expression in acquired immune deficiency and lymphadenopathy syndromes. J Immunol. 1984 Sep;133(3):1313–1317. [PubMed] [Google Scholar]
  18. Reem G. H., Yeh N. H. Interleukin 2 regulates expression of its receptor and synthesis of gamma interferon by human T lymphocytes. Science. 1984 Jul 27;225(4660):429–430. doi: 10.1126/science.6429853. [DOI] [PubMed] [Google Scholar]
  19. Reeves W. G., Zamkoff K. W., Poiesz B. J., Paolozzi F. P., Tomar R. H., Moore J. L., Ruscetti F. W. T cell growth factor required for optimal induction of T cell growth factor receptor expression in phytohemagglutinin-stimulated T cells. J Biol Response Mod. 1985 Feb;4(1):83–95. [PubMed] [Google Scholar]
  20. Robb R. J., Greene W. C., Rusk C. M. Low and high affinity cellular receptors for interleukin 2. Implications for the level of Tac antigen. J Exp Med. 1984 Oct 1;160(4):1126–1146. doi: 10.1084/jem.160.4.1126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schulof R. S. Thymic peptide hormones: basic properties and clinical applications in cancer. Crit Rev Oncol Hematol. 1985;3(4):309–376. doi: 10.1016/s1040-8428(85)80035-4. [DOI] [PubMed] [Google Scholar]
  22. Shoham J., Eshel I. 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 Immunopharmacol. 1983;5(6):515–522. doi: 10.1016/0192-0561(83)90044-9. [DOI] [PubMed] [Google Scholar]
  23. Smith K. A., Cantrell D. A. Interleukin 2 regulates its own receptors. Proc Natl Acad Sci U S A. 1985 Feb;82(3):864–868. doi: 10.1073/pnas.82.3.864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sztein M. B., Goldstein A. L. Thymic hormones--a clinical update. Springer Semin Immunopathol. 1986;9(1):1–18. doi: 10.1007/BF00201901. [DOI] [PubMed] [Google Scholar]
  25. Talmadge J. E., Benedict K. L., Uithoven K. A., Lenz B. F. The effect of experimental conditions on the assessment of T cell immunomodulation by biological response modifiers (thymosin fraction five). Immunopharmacology. 1984 Feb;7(1):17–26. doi: 10.1016/0162-3109(84)90004-3. [DOI] [PubMed] [Google Scholar]
  26. Uchiyama T., Nelson D. L., Fleisher T. A., Waldmann T. A. A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T cells. II. Expression of Tac antigen on activated cytotoxic killer T cells, suppressor cells, and on one of two types of helper T cells. J Immunol. 1981 Apr;126(4):1398–1403. [PubMed] [Google Scholar]
  27. Umiel T., Pecht M., Trainin N. THF, a thymic hormone, promotes interleukin-2 production in intact and thymus-deprived mice. J Biol Response Mod. 1984 Aug;3(4):423–434. [PubMed] [Google Scholar]
  28. Welte K., Andreeff M., Platzer E., Holloway K., Rubin B. Y., Moore M. A., Mertelsmann R. Interleukin 2 regulates the expression of Tac antigen on peripheral blood T lymphocytes. J Exp Med. 1984 Nov 1;160(5):1390–1403. doi: 10.1084/jem.160.5.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Zatz M. M., Goldstein A. L. Mechanism of action of thymosin. I. Thymosin fraction 5 increases lymphokine production by mature murine T cells responding in a mixed lymphocyte reaction. J Immunol. 1985 Feb;134(2):1032–1038. [PubMed] [Google Scholar]
  30. Zatz M. M., Oliver J., Samuels C., Skotnicki A. B., Sztein M. B., Goldstein A. L. Thymosin increases production of T-cell growth factor by normal human peripheral blood lymphocytes. Proc Natl Acad Sci U S A. 1984 May;81(9):2882–2885. doi: 10.1073/pnas.81.9.2882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Zatz M. M., Oliver J., Sztein M. B., Skotnicki A. B., Goldstein A. L. Comparison of the effects of thymosin and other thymic factors on modulation of interleukin-2 production. J Biol Response Mod. 1985 Aug;4(4):365–376. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES