Interleukin-1 Induced T-Lymphocyte Proliferation and Its Relation to IL-1 Receptors

  • Charles A. Dinarello
  • Scott F. Orencole
  • Nerina Savage


Interleukin-1 (IL-1) is a polypeptide cytokine which possesses several biological properties including lymphocyte activation, fever, endothelial cell stimulation and mesenchymal tissue remodeling (reviewed in 1). In lymphocytes, fibroblasts, endothelial cells, and macrophages, IL-1 induces a variety of immunomodulatory molecules, such as more IL-2, granulocyte-macrophage colony stimulating factor, IL-6, and IL-1 itself.2 Many of the biological properties of IL-1 are also observed with another polypeptide cytokine, tumor necrosis factor (TNF)3; however, IL-1 and TNF have distinct primary structures and cell receptors. IL-1 receptors are most numerous on fibroblasts4 and T-cell lines.5–7 These include the EL4 murine thymoma and LBRM line. The IL-1 cell surface binding protein (receptor) recognizes both beta and alpha forms of IL-I has been demonstrated on several lymphocyte-derived cell lines as well as mature, circulating blood T-cells.8


Proliferative Response Parent Clone Autocrine Growth Factor High Affinity Binding Site CTLL Cell 
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  1. 1.
    C.A. Dinarello, The biology of interleukin-1, FASEB J 2: 108 (1988).Google Scholar
  2. 2.
    C.A. Dinarello, T. Ikejima, S.J.C. Warner, S.F. Orencole, G. Lonnemann, J.G. Cannon, and P. Libby, Interleukin-1 induces interleukin-1. I. Induction of circulating interleukin-1 in rabbits in vivo and in human mononuclear cells in vitro J immunol 139: 1902 (1987).Google Scholar
  3. 3.
    B. Beutler and A. Cerami, Cachectin and tumor necrosis factor as two sides of the same biolocial coin, Nature 320: 584 (1986).Google Scholar
  4. 4.
    T.A. Bird, A.J.H. Gearing, and J. Saklatvala, Murine interleukin-1 receptor: difference in binding properties between fibroblastic and thymoma cells and evidence for a two-chain receptor model, FEBS Lett 225: 21 (1987).Google Scholar
  5. 5.
    P.O. Kilian, K.L. Kaffka, A.S. Stern, D. Woehle, W.R. Benjamin, T.M. DeChiara, U. Gubler, J.J. Farrar, S.B. Mizel, and P.T. Lomedico, Interleukin-1-alpha and interleukin-1-beta bind to the same receptor on T cells, J Immunol 136: 4509 (1986).Google Scholar
  6. 6.
    J.W. Lowenthal and H.R. MacDonald, Binding and internalization of interleukin-1 by T cells. Direct evidence for high and low affinity classes of interleukin-1 receptor, J Exp Med 164: 1060 (1986).Google Scholar
  7. 7.
    K. Matsushima, J. Yodoi, Y. Tagaya and J.J. Oppenheim, Down-regulation of interleukin-1 (IL-1) receptor expression by IL-1 and fate of internalized 1251-labeled IL-1-beta in a human large granular lymphocyte cell line, J Immunol 137: 3183 (1986).PubMedGoogle Scholar
  8. 8.
    F. Shirakawa, Y. Tanaka, T. Ota, H. Suzuki, S. Eto, and U. Yamashita, Expression of interleukin-1 receptors on human peripheral T cells, J Immunol 138: 4243 (1987).Google Scholar
  9. 9.
    S.B. Mizel, Interleukin-1 and T cell activation, Immunol Rev 63: 51 (1982).Google Scholar
  10. 10.
    S.K. Durum, J.A. Schmidt, and J.J. Oppenheim, Interleukin-1: an immunological perspective. Ann Rev Immunol 3: 263 (1985).CrossRefGoogle Scholar
  11. T. Krakauer, D. Mizel, and J.J. Oppenheim, Independent and synergistic thymocyte proliferative activities of PMA and IL-1, J. Immunol. 129:939 (1982).Google Scholar
  12. 12.
    P.L. Simon, Calcium mediates one of the signals required for interleukin-1 and 2 production by murine cell lines, Cell Immunol 87: 720 (1984).Google Scholar
  13. 13.
    K.A. Smith, L.B. Lachman, J.J. Oppenheim, and M.F. Favata, The functional relationship of the interleukins J Exp Med 151: 1551 (1980).Google Scholar
  14. J.M. Williams, D. DeLoria, J.A. Hansen, C.A. Dinarello, R. Loertxcher, H.M. Shapiro, and T.B. Strom, The events of primary T cell activation can be staged by use of sepharose-bound anti-T3 (64.1) monoclonal antibody and purified interleukin-1, J. Immunol. 135:2249 (1985).Google Scholar
  15. J. Kaye, S. Gillis, S.B. Mizel, E.M. Shevach, T.R. Malek, C.A. Dinarello, L.B. Lachman, and C.A. Janeway, 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. 133:1339 (1984).Google Scholar
  16. A.H. Lichtman, E.A. Kurt-Jones, and A.K. Abbas, B cell stimulatory factor 1 and not interleukin-2 is the autocrine growth factor for some helper T lymphocytes, Proc. Natl. Acad. Sci. USA 84:824 (1987).Google Scholar
  17. 17.
    T. Kupper, M. Horowitz, F. Lee, R. Robb and P.M. Flood, Autocrine growth of T cells independent of interleukin-2: identification of interleukin-4 (IL-4, BSF-1) as an autocrine growth factor for a cloned antigen-specific helper T cell. J. Immunol. 138: 4280.Google Scholar
  18. T. Kupper, P. Flood, D. Coleman, and M. Horowitz, Growth of an interleukin 2/interleukin 4-dependent T cell line induced by granulocyte-macrophage colony-stimulating factor (GM-CSF), J. Immunol. 138:4288 (1987).Google Scholar
  19. 19.
    G. Lonnemann, S. Endres, J.W.M. van der Meer, J.G. Cannon, and C.A. Dinarello, A radioimmunoassay for production from human mononuclear cells. Lymphokine Res. (in press).Google Scholar
  20. 20.
    J. Ohara and W.E. Paul, Production of a monoclonal antibody to and molecular characterization of B-cell stimulating factor-1, Nature 315: 333 (1985).Google Scholar
  21. 21.
    A. Billiau, BSF-2 is not just a differentiation factor, Nature 324: 415 (1986).PubMedGoogle Scholar
  22. 22.
    J.W. Lowenthal, J.-C. Cerottini, and H.R. MacDonald, Interleukin-1 dependent induction of both interleukin-2 secretion and interleukin-2 receptor expression by thymoma cells, J Immunol 137: 1226 (1986).Google Scholar
  23. 23.
    B. Tartakovsky, E.J. Kovacs, L. Takacs, and S.K. Durum, T cell clone producing an IL-1-like activity after stimulation by antigen-presenting B cells. J. Immunol. 137:160 (1986).Google Scholar
  24. 24.
    D.L. Lacey, J. Axelrod, J.C. Chappel, A.J. Kahn, and S.L. Teitelbaum, Vitamin D affects proliferation of a murine T helper cell clone, J. Immunol. 138:1680 (1987).Google Scholar
  25. 25.
    D.L. Ennist, K.L. Elkins, S.C. Cheng, and M. Howard, Activity of a partially purified human BCGF on murine assays for B cell stimulatory factors. II. Synergy between two distinct BCGF II-like factors in promoting B cell differentiation, J. Immunol. 139: 1525 (1987).PubMedGoogle Scholar
  26. 26.
    S. Ho, R.T. Abraham, A. Nilson, B.S. Handwerger, and D.J. McKean, Interleukin-lmediated activation of interleukin-4 producing T lymphocytes. Proliferation by IL-4-dependent and IL-4-independent mechanisms. J. Immunol. 139:1532 (1987).Google Scholar
  27. 27.
    A.H. Lichtman, M.E. Williams, J. Ohara, W.E. Paul, D.V. Faller, and A.K. Abbas, Retrovirus infection alters growth factor responses of T lymphocytes, L Immunol. 138: 3276 (1987).Google Scholar
  28. 28.
    D.L. Lacey, J.C. Chappel, S.L. Teitelbaum, Interleukin-1 stimulates proliferation of a nontransformed T lymphocyte line in the absence of co-mitogen, J. Immunol. 139:2649 (1987).Google Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Charles A. Dinarello
    • 1
    • 2
  • Scott F. Orencole
    • 1
    • 2
  • Nerina Savage
    • 1
    • 2
  1. 1.Department of MedicineTufts University School of Medicine and New England Medical Center HospitalBostonUSA
  2. 2.Department of Medical BiochemistryMedical School, University of the Witwatersrand JohannesburgSouth Africa

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