Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1992 Jan;87(1):150–156. doi: 10.1111/j.1365-2249.1992.tb06429.x

Regulation of IL-2 beta receptor expression and beta-chain mRNA by human thymocytes.

G H Reem 1, X Han 1, A Marcelli 1
PMCID: PMC1554230  PMID: 1733630

Abstract

The high affinity form of the human IL-2 receptor (IL-2R) has two known components, the IL-2R alpha (p55) and the IL-2R beta chain (p75). We have previously shown that recombinant IL-2 (rIL-2) could induce the expression of the alpha-chain (p55) on T cells and thymocytes, and increase this expression following suboptimal activation with concanavalin A (Con A) in combination with IL-2. An increase in the accumulation of IL-2R alpha-specific mRNA induced by rIL-2 in T cells and thymocytes had also been documented. We report here that the expression of IL-2R beta on the cell surface can be demonstrated on human thymocytes by the binding of Mik beta1, a MoAb directed against an epitope of the beta-chain. The IL-2R beta chain is constitutively expressed on freshly isolated thymocytes; this expression can be increased in thymocytes activated with Con A in combination with IL-2 or tetradecanoylphorbol 13-acetate (TPA). Blocking the formation of high affinity receptors with a MoAb directed against the alpha-chain of the receptor results in an increase in the display of IL-2R beta as evidenced by binding of MoAb Mik beta1. The accumulation of IL-2R-beta-specific mRNA is observed in freshly isolated thymocytes and it is increased in thymocytes cultured with rIL-2 alone, with Con A, and further enhanced by the addition of rIL-2 in combination with Con A or with TPA. Cyclosporine (CsA), which inhibits the accumulation of lymphokine-specific mRNA of thymocytes, does not inhibit the induction of the accumulation of IL-2R beta-specific mRNA. This is analogous to its effect on the expression of the alpha-chain (p55), and the accumulation of alpha-chain-specific mRNA.

Full text

PDF
150

Images in this article

Selected References

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

  1. Allouche M., Sahraoui Y., Augery-Bourget Y., Ohashi Y., Sugamura K., Jasmin C., Georgoulias V. Presence of a p70 IL-2-binding peptide on leukemic cells from various hemopoietic lineages. J Immunol. 1989 Oct 1;143(7):2223–2229. [PubMed] [Google Scholar]
  2. Colamonici O. R., Rosolen A., Cole D., Kirsch I., Felix C., Poplack D. G., Neckers L. M. Stimulation of the beta-subunit of the IL-2 receptor induces MHC-unrestricted cytotoxicity in T acute lymphoblastic leukemia cells and normal thymocytes. J Immunol. 1988 Aug 15;141(4):1202–1205. [PubMed] [Google Scholar]
  3. Dukovich M., Wano Y., Le thi Bich Thuy, Katz P., Cullen B. R., Kehrl J. H., Greene W. C. A second human interleukin-2 binding protein that may be a component of high-affinity interleukin-2 receptors. Nature. 1987 Jun 11;327(6122):518–522. doi: 10.1038/327518a0. [DOI] [PubMed] [Google Scholar]
  4. Greene W. C., Leonard W. J. The human interleukin-2 receptor. Annu Rev Immunol. 1986;4:69–95. doi: 10.1146/annurev.iy.04.040186.000441. [DOI] [PubMed] [Google Scholar]
  5. Hatakeyama M., Mori H., Doi T., Taniguchi T. A restricted cytoplasmic region of IL-2 receptor beta chain is essential for growth signal transduction but not for ligand binding and internalization. Cell. 1989 Dec 1;59(5):837–845. doi: 10.1016/0092-8674(89)90607-7. [DOI] [PubMed] [Google Scholar]
  6. Hatakeyama M., Tsudo M., Minamoto S., Kono T., Doi T., Miyata T., Miyasaka M., Taniguchi T. Interleukin-2 receptor beta chain gene: generation of three receptor forms by cloned human alpha and beta chain cDNA's. Science. 1989 May 5;244(4904):551–556. doi: 10.1126/science.2785715. [DOI] [PubMed] [Google Scholar]
  7. Nishi M., Ishida Y., Honjo T. Expression of functional interleukin-2 receptors in human light chain/Tac transgenic mice. Nature. 1988 Jan 21;331(6153):267–269. doi: 10.1038/331267a0. [DOI] [PubMed] [Google Scholar]
  8. Ohashi Y., Takeshita T., Nagata K., Mori S., Sugamura K. Differential expression of the IL-2 receptor subunits, p55 and p75 on various populations of primary peripheral blood mononuclear cells. J Immunol. 1989 Dec 1;143(11):3548–3555. [PubMed] [Google Scholar]
  9. Reem G. H., Duggan A., Schleuning M. Immunoregulation and production of tumor necrosis factor alpha by human thymocytes. Cancer Res. 1989 Jul 1;49(13):3568–3573. [PubMed] [Google Scholar]
  10. Reem G. H., Yeh N. H. Modulation of the expression of interleukin 2 receptors of human thymocytes by recombinant interleukin 2. Arch Biochem Biophys. 1985 Jun;239(2):455–461. doi: 10.1016/0003-9861(85)90711-8. [DOI] [PubMed] [Google Scholar]
  11. Reem G. H., Yeh N. H. Regulation by interleukin 2 of interleukin 2 receptors and gamma-interferon synthesis by human thymocytes: augmentation of interleukin 2 receptors by interleukin 2. J Immunol. 1985 Feb;134(2):953–958. [PubMed] [Google Scholar]
  12. Reem G. H., Yeh N. H., Urdal D. L., Kilian P. L., Farrar J. J. Induction and upregulation by interleukin 2 of high-affinity interleukin 2 receptors on thymocytes and T cells. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8663–8666. doi: 10.1073/pnas.82.24.8663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Robb R. J., Rusk C. M., Yodoi J., Greene W. C. Interleukin 2 binding molecule distinct from the Tac protein: analysis of its role in formation of high-affinity receptors. Proc Natl Acad Sci U S A. 1987 Apr;84(7):2002–2006. doi: 10.1073/pnas.84.7.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Saragovi H., Malek T. R. Evidence for additional subunits associated to the mouse interleukin 2 receptor p55/p75 complex. Proc Natl Acad Sci U S A. 1990 Jan;87(1):11–15. doi: 10.1073/pnas.87.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  17. Takeshita T., Goto Y., Tada K., Nagata K., Asao H., Sugamura K. Monoclonal antibody defining a molecule possibly identical to the p75 subunit of interleukin 2 receptor. J Exp Med. 1989 Apr 1;169(4):1323–1332. doi: 10.1084/jem.169.4.1323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Toribio M. L., Gutiérrez-Ramos J. C., Pezzi L., Marcos M. A., Martínez C. Interleukin-2-dependent autocrine proliferation in T-cell development. Nature. 1989 Nov 2;342(6245):82–85. doi: 10.1038/342082a0. [DOI] [PubMed] [Google Scholar]
  19. Tsudo M., Goldman C. K., Bongiovanni K. F., Chan W. C., Winton E. F., Yagita M., Grimm E. A., Waldmann T. A. The p75 peptide is the receptor for interleukin 2 expressed on large granular lymphocytes and is responsible for the interleukin 2 activation of these cells. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5394–5398. doi: 10.1073/pnas.84.15.5394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Tsudo M., Karasuyama H., Kitamura F., Nagasaka Y., Tanaka T., Miyasaka M. Reconstitution of a functional IL-2 receptor by the beta-chain cDNA. A newly acquired receptor transduces negative signal. J Immunol. 1989 Dec 15;143(12):4039–4043. [PubMed] [Google Scholar]
  21. Tsudo M., Karasuyama H., Kitamura F., Tanaka T., Kubo S., Yamamura Y., Tamatani T., Hatakeyama M., Taniguchi T., Miyasaka M. The IL-2 receptor beta-chain (p70). Ligand binding ability of the cDNA-encoding membrane and secreted forms. J Immunol. 1990 Jul 15;145(2):599–606. [PubMed] [Google Scholar]
  22. Tsudo M., Kitamura F., Miyasaka M. Characterization of the interleukin 2 receptor beta chain using three distinct monoclonal antibodies. Proc Natl Acad Sci U S A. 1989 Mar;86(6):1982–1986. doi: 10.1073/pnas.86.6.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tsudo M., Kozak R. W., Goldman C. K., Waldmann T. A. Contribution of a p75 interleukin 2 binding peptide to a high-affinity interleukin 2 receptor complex. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4215–4218. doi: 10.1073/pnas.84.12.4215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Tsudo M., Kozak R. W., Goldman C. K., Waldmann T. A. Demonstration of a non-Tac peptide that binds interleukin 2: a potential participant in a multichain interleukin 2 receptor complex. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9694–9698. doi: 10.1073/pnas.83.24.9694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Waldmann T. A. The structure, function, and expression of interleukin-2 receptors on normal and malignant lymphocytes. Science. 1986 May 9;232(4751):727–732. doi: 10.1126/science.3008337. [DOI] [PubMed] [Google Scholar]
  26. Yeh N. H., Dipre M., Reem G. H. Modulation of the expression of Tac antigen (T-cell growth factor response) on human thymocytes. Thymus. 1984;6(4):255–261. [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES