Skip to main content
SpringerLink
Log in

Making sense of the combined effect of interleukin-2 and interleukin-4 on lymphocytes using a mathematical model

  • Published:
Bulletin of Mathematical Biology Aims and scope Submit manuscript

Abstract

The cytokines are the information superhighway of the immune system. They are an important component of the integrated behavior of the system. In order to be able to have a good understanding of the immune system, we must be able to model the effect of cytokines and their combined effect. This work is a step in that direction. We study the combined effect of two cytokines: interleukin-2 (IL-2) and interleukin-4 (IL-4) on some cells of the immune system.

Interleukin-2 and interleukin-4 are important growth and differentiation factors for B and T cells. Interleukin-4 antagonizes the effect of interleukin-2 on B cells and some T cells while it synergizes with interleukin-2 on other T cells. We build a mathematical model of the interaction of both cytokines on T and B cells as a building block toward a model of the Th1/Th2 cross-regulation. The response of a given cell to the combination of interleukin-2 and interleukin-4 is shown to involve competing dynamical effects which can lead to either antagnostic or synergistic combined effect.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Burke, M., B. Morel, T. Orris, J. Bray, S. McCarthy, P. Morel. 1995. In preparation.

  • Cantor, H. and E. A. Boyse. 1975.J. Exp. Med. 141, 1376–1389.

    Article  Google Scholar 

  • Cantrell, D. A. and K. A. Smith. 1984.Science 224, 1312–1316.

    Google Scholar 

  • Casey, L. S., A. H. Lichtman, and M. Boothby. 1992.J. Immunol. 148, 3418–3426.

    Google Scholar 

  • Cher, D. J. and T. R. Mosmann. 1987.J. Immunol. 138, 3688–3694.

    Google Scholar 

  • Defrance, T., B. Vanbervliet, J. P. Aubry, and J. Banchereau. 1988.J. Exp. Med. 168, 1321–1337.

    Article  Google Scholar 

  • Duprez, V., V. Cornet, and A. Dautry-Varsat. 1988.J. Biol. Chem. 263, 12860–12865.

    Google Scholar 

  • Fernandez-Botran, R., V. M. Sanders, T. R. Mossman, and E. S. Vitetta. 1988.J. Exp. Med. 168, 543–558.

    Article  Google Scholar 

  • Fernandez-Botran, R., V. M. Sanders, and E. S. Vitetta. 1989.J. Exp. Med. 169, 379–391.

    Article  Google Scholar 

  • Fiorentino, D. F., M. W. Bond, and T. R. Mosmann. 1989.J. Exp. Med. 170, 2081–2095.

    Article  Google Scholar 

  • Gajewski, T. F. and F. W. Fitch. 1988.J. Immunol. 140, 4245–4252.

    Google Scholar 

  • Gaya, A., O. de la Calle, J. Yague, E. Alsinet, M. D. Fernandez, M. Romero, V. Fabregat, J. Mortorell, and J. Vives. 1991.J. Immunol. 146, 4209–4214.

    Google Scholar 

  • Ishida, H., G. Yang, N. Harada, R. L. Hastings, B. E. Castle, R. Kastelein, A. Miyajima, and M. Howard. 1991.Cell. Immunol. 136, 142–154.

    Article  Google Scholar 

  • Jelinek, D. F. and P. E. Lipsky. 1988.J. Immunol. 141, 164–173.

    Google Scholar 

  • Kalagnama, J. R., D. J. Tweardy, S. A. McCarthy, P. A. Morel and B. F. Morel. Pittsburgh Cancer Institute Report, 1995.

  • Karray, S., T. Defrance, H. Merle-Beral, J. Banchereau, P. Debre, and P. Galanaud. 1988.J. Exp. Med. 168, 85–94.

    Article  Google Scholar 

  • Karray, S., A. Dautry-Varsat, M. Tsudo, H. Merle-Beral, P. Debre, and P. Galanaud. 1990.J. Immunol. 145, 1152–1158.

    Google Scholar 

  • Katsura, Y. 1977.Immunology,32, 227–235.

    Google Scholar 

  • Kawakami, Y., M. C. Custer, S. A. Rosenberg, and M. T. Lotze. 1989.J. Immunol. 142, 3452–3461.

    Google Scholar 

  • Lee, H.-K., X. Xia, and Y. S. Choi. 1990.J. Immunol. 144, 3431–3436.

    Google Scholar 

  • Loewe, S. 1957.Pharmacol. Rev. 9, 237–244.

    Google Scholar 

  • Lowenthal, J. W., B. E. Castle, J. Christiansen, J. Schreurs, D. Rennick, N. Arai, P. Hoy, Y. Takebe, and M. Howard. 1988.J. Immunol. 140, 456–464.

    Google Scholar 

  • Martinez, O. M., R. S. Gibbons, M. R. Garovoy, and F. R. Aronson. 1990.J. Immunol. 144, 2211–2215.

    Google Scholar 

  • Miller, C. L., J. W. Hooton, S. Gillis, and V. Paetkau. 1990.J. Immunol. 144, 1331–1337.

    Google Scholar 

  • Mitchell, L. C., L. S. Davis, and P. E. Lipsky. 1989.J. Immunol. 142, 1548–1557.

    Google Scholar 

  • Mosmann, T. R. and R. L. Coffman. 1989.Ann. Rev. Immunol. 7, 145–173.

    Article  Google Scholar 

  • Mosmann, T. R., H. Cherwinski, M. W. Bond, M. A. Giedlin, and R. L. Coffman. 1986.J. Immunol. 136, 2348–2357.

    Google Scholar 

  • Parish, C. R. 1972.Transplant Rev. 13, 35–66.

    Google Scholar 

  • Paul, W. E. and J. Ohara. 1987.Ann. Rev. Immunol. 5, 429–459.

    Google Scholar 

  • Perelson, A. 1991. InTheory and Control of Dynamical Systems, S. Anderson, (Ed.), World Scientific Publishing, River Edge, NJ.

    Google Scholar 

  • Smith, K. A. 1988.Science 240, 1169–1176.

    Google Scholar 

  • Smith, K. A. 1989.Ann. Rev. Cell. Biol. 5, 397–425.

    Google Scholar 

  • Spits, H., H. Yssel, Y. Takebe, N. Arai, T. Yokota, F. Lee, K. Arai, J. Banchereau, and J. E. de Vries. 1987.J. Immunol. 139, 1142–1147.

    Google Scholar 

  • Splawski, J. B., D. F. Jelinek, and P. E. Lipsky. 1989.J. Immunol. 142, 1569–1575.

    Google Scholar 

  • Stevens, T. L., A. Bossie, V. M. Sanders, R. Fernandez-Botran, R. L. Coffman, T. R. Mosmann, and E. S. Vitetta. 1988.Nature 334, 255–258.

    Article  Google Scholar 

  • Takeshita, T., H. Asao, K. Ohtani, N. Ishii, S. Kumaki, N. Tanaka, H. Munakata, M. Nakamura, and K. Sugamura. 1992.Science 257, 379–382.

    Google Scholar 

  • Vasquez, A., S. Mills, and A. Maizel. 1989.J. Immunol. 142, 94–99.

    Google Scholar 

  • Watson, J. 1979.J. Exp. Med. 150, 1510–1519.

    Article  Google Scholar 

  • Zubler, R. H., J. W. Lowenthal, F. Erard, N. Hashimoto, R. Devos, and H. R. MacDonald. 1984.J. Exp. Med. 160, 1170–1183.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physics, Carnegie Mellon University, 15213, Pittsburgh, PA, USA

    Benoît F. Morel

  2. Department of Engineering and Public Policy, Carnegie Mellon University, 15213, Pittsburgh, PA, USA

    Benoît F. Morel, Jayant Kalagnanam & David J. Tweardy

  3. Pittsburgh Cancer Institute, University of Pittsburgh, 15213, Pittsburgh, PA, USA

    Meghan A. Burke & Penelope A. Morel

  4. Department of Surgery, University of Pittsburgh School of Medicine, 15213, Pittsburgh, PA, USA

    Susan A. McCarthy

  5. Department of Medicine, University of Pittsburgh School of Medicine, 15213, Pittsburgh, PA, USA

    David J. Tweardy & Penelope A. Morel

  6. Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, 15213, Pittsburgh, PA, USA

    Meghan A. Burke, Susan A. McCarthy, David J. Tweardy & Penelope A. Morel

Authors
  1. Benoît F. Morel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Meghan A. Burke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jayant Kalagnanam
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Susan A. McCarthy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David J. Tweardy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Penelope A. Morel
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Author to whom correspondence should be addressed at Department of Engineering and Public Policy. Work supported by NIH grant nv: Ai31427.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Morel, B.F., Burke, M.A., Kalagnanam, J. et al. Making sense of the combined effect of interleukin-2 and interleukin-4 on lymphocytes using a mathematical model. Bltn Mathcal Biology 58, 569–594 (1996). https://doi.org/10.1007/BF02460597

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02460597

Keywords

Search

Navigation