Journal of Clinical Immunology

, Volume 6, Issue 2, pp 114–120 | Cite as

An analysis of the cellular requirements for the production of soluble interleukin-2 receptorsin vitro

  • David L. Nelson
  • Laurence A. Rubin
  • Carole C. Kurman
  • Mary E. Fritz
  • Bernard Boutin
Original Articles


Following activationin vitro, peripheral blood mononuclear cells (PBMC) express cell-associated interleukin-2 receptors (IL-2R) and also release soluble IL-2R into culture supernatants. The present studies were undertaken to define which normal cells were responsible for the release of soluble IL-2Rin vitro. Both cell-associated and soluble IL-2R were quantitatively measured with a “sandwich” enzyme-linked immunoassay employing two monoclonal antibodies. PBMC were separated into populations of surface immunoglobulin-negative cells (T cells and monocytes) and surface immunoglobulin-positive cells (B cells and monocytes), and the T-cell population was further separated into OKT4-positive (OKT4+) cells and OKT4-negative (OKT4) cells. Following activation with phytohemagglutinin, pokeweed mitogen, and the monoclonal antibody OKT3, large amounts of soluble IL-2R were released by PBMC, unseparated T cells, OKT4+ T cells, and OKT4 T cells. The population containing B cells and monocytes made small but readily detectable amounts of soluble IL-2R when stimulated with these T-cell mitogens; likely the result of contaminating T cells in the population. However, when highly purified B cells were stimulated withStaphylococcus aureus Cowan and recombinant IL-2, they also released small amounts of soluble IL-2R. The release of soluble IL-2R by T cells appeared monocyte dependent when OKT3, but not phytohemagglutinin, was employed for activation, and monocytes themselves released no detectable IL-2R under the conditions employed. These studies define the cellular requirements for the release of soluble IL-2Rin vitro and demonstrate that such receptors are released by B cells, T cells, and both OKT4+ and OKT4 T-cell subsets.

Key words

Interleukin-2 interleukin-2 receptor lymphocyte subsets lymphocyte activation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Cantrell DA, Smith KA: The interleukin-2 T-cell system: A new cell growth model. Science 224:1312–1316, 1984Google Scholar
  2. 2.
    Leonard WJ, Depper JM, Robb RJ, Waldmann TA, Greene WC: Characterization of the human receptor for T cell growth factor. Proc Natl Acad Sci USA 80:6957–6961, 1983Google Scholar
  3. 3.
    Tsudo M, Uchiyama T, Uchino H: Expression of Tac antigen on activated normal human B cells. J Exp Med 160:612–617, 1984Google Scholar
  4. 4.
    Waldmann TA, Goldman CK, Robb RJ, Depper JM, Leonard WJ, Sharrow SO, Bongiovanni KF, Korsmeyer SJ, Greene WC: Expression of interleukin-2 receptors on activated B cells. J Exp Med 160:1450–1466, 1984Google Scholar
  5. 5.
    Moll H, Emmrich F, Simon MM: Recombinant human interleukin 2 directly provides signals for the proliferation and functional maturation of murine B lymphocytes. Immunobiology 169:447–454, 1985Google Scholar
  6. 6.
    Rubin LA, Kurman CC, Fritz ME, Biddison WE, Boutin B, Yarchoan R, Nelson DL: Soluble interleukin-2 receptors are released from activated human lymphoid cellsin vitro. J Immunol 135:3172–3177, 1985Google Scholar
  7. 7.
    Rubin LA, Kurman CC, Fritz ME, Nelson DL: Serum levels of soluble interleukin-2 receptor are elevated in patients with certain lymphoreticular malignancies. Clin Res 33:457A, 1985Google Scholar
  8. 8.
    Uchiyama T, Broder S, Waldmann TA: A monoclonal antibody reactive with activated and functionally mature human T cells. J Immunol 126:1393–1397, 1981Google Scholar
  9. 9.
    Rubin LA, Kurman CC, Biddison WE, Goldman ND, Nelson DL: A monoclonal antibody, 7G7/B6, that binds to an epitope on the human IL-2 receptor distinct from that recognized by IL-2 or anti-Tac. Hybridoma 4:91–102, 1985Google Scholar
  10. 10.
    Shaw S, Nelson DL, Shearer GM: Human cytotoxic responsein vitro to trinitrophenyl-modified autologous cells. I. T-cell recognition of TNP in association with widely shared antigens. J Immunol 121:281–289, 1978Google Scholar
  11. 11.
    Nelson DL, Bundy BM, Pitchon HE, Blaese RM, Strober W: The effector cells in human peripheral blood mediating mitogen-induced cellular cytotoxicity and antibody-dependency cellular cytotoxicity. J Immunol 117:1472–1481, 1976Google Scholar
  12. 12.
    Uchiyama T, Nelson DL, Fleisher TA, Waldmann TA: 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 26:1398–1403, 1981Google Scholar
  13. 13.
    Kirchner H, Tosato G, Blaese RM, Broder S, Magrath, IT: Polyclonal immunoglobulin secretion by human B lymphocytes exposed to Epstein-Barr virusin vitro. J Immunol 122:1310–1313, 1979Google Scholar
  14. 14.
    Chien MM, Ashman RF: Rapid separation of human monocytes and lymphocytes by Sephadex G-10. J Immunol Methods 71:25–36, 1984Google Scholar
  15. 15.
    Yarchoan R, Barrow LA, Kurman CC, Strober W, Nelson DL: Human peripheral blood mononuclear cells produce IgA antiinfluenza virus antibody in a secondaryin vitro antibody response. J Immunol 135:1033–1039, 1985Google Scholar
  16. 16.
    Bundy BM: Studies of the Requirement for Adherent Cells as Accessory Cells in the Specific Cytotoxic Response of the Human Mixed Lymphocytes Culture PhD thesis. Washington, DC, George Washington University, 1982Google Scholar
  17. 17.
    Herrmann F, Cannistra SA, Levine H, Griffin JD: Expression of IL-2 receptors and binding of IL-2 by gamma-interferon induced human leukemic and normal monocytic cells. J Exp Med 162:1111–1114, 1985Google Scholar

Copyright information

© Plenum Publishing Corporation 1986

Authors and Affiliations

  • David L. Nelson
    • 1
  • Laurence A. Rubin
    • 1
  • Carole C. Kurman
    • 1
  • Mary E. Fritz
    • 1
  • Bernard Boutin
    • 1
  1. 1.Immunophysiology Section, Metabolism Branch, National Cancer InstituteNational Institutes of HealthBethesda

Personalised recommendations