Skip to main content
SpringerLink
Log in

Antigen/Mitogen Induced Cytolytic Activity and IL-2 Secretion in Memory-Like CTL-Hybridomas

  • Chapter
  • First Online:
Mechanisms of Cell-Mediated Cytotoxicity II

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 184))

Summary

Memory-like monoclonal CTL hybridomas, derived from fusion of the AKR thymoma BW5147 with secondary CTL generated in vivo or in MLC cultures, have been used to study the mechanism whereby antigen/mitogen induces anamnestic CTL responses. Specifically, we have asked whether induction of cytolytic activity can be promoted by an antigenic/mitogenic signal without involvement of IL-2 receptors, IL-2, or other extrinsic factors. We have found that antigen/lectin alone can trigger the cytolytic potential of the hybridomas and induce IL-2 secretion. Pure IL-2 and conditioned medium were ineffective inducers of cytotoxicity. Moreover, IL-2 receptors were not detected on the hybrid cells before and after antigenic stimulation, demonstrating that expression of IL-2 receptors and induction of specific killing activity are not genetically linked. Non-activated and activated cells conjugated with target cells equally well, suggesting that induction of cytolytic activity involves a post target cell binding step. Close linkage between cytotoxicity and IL-2 secretion has been observed: induction of killing was consistently associated with IL-2 secretion and stimulation of both activities could be blocked by Cyclosporin A. IL-2 was secreted by the CTL hybrids as early as 3 h following stimulation. We propose that the immediate supply of IL-2 by such memory CTL enhances antigenic response of other, IL-2-dependent T cells.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. MacDonald, H. R. 1982. Differentiation of cytolytic T lymphocytes. Immunol. Today 3: 183.

    Google Scholar 

  2. Larsson, E.L., Gullberg, M., Beretta, A., and Coutinho, A. 1982. Requirement for the involvement of clonally distributed receptors in the activation of cytotoxic T lymphocytes. Immunol. Rev. 68:67.

    Article  CAS  Google Scholar 

  3. Nabholz, M. and MacDonald, H. R. 1983. Cytolytic T lymphocytes. Ann. Rev. Immunol. 1:273.

    Article  CAS  Google Scholar 

  4. Möller, G. (ed.) 1980. T cell stimulating growth factors. Immunol. Rev. 51:1–357.

    Google Scholar 

  5. Von Boehmer, H. and Turton, K. 1983. Autonomously proliferating K/D-restricted cytolytic T cell clones. Eur.J. Immunol. 13:176.

    Article  Google Scholar 

  6. Andrus, L., Granelli-Piperno, A., and Reich, E. 1984. Cytotoxic T cells both produce and respond to interleukin 2. J. Exp. Med. 59, 647.

    Article  Google Scholar 

  7. Lefrancois, L., Klein, J.R., Patkau, V. and Bevan, M.J. 1984. An big en-independent activation of memory cytotoxic T cells by interleukin 2. J. Immunol. 132: 1845.

    CAS  PubMed  Google Scholar 

  8. Conzelman, A., Corthesy, P., Cianfriglia, M., Silva, A., and Nabholz, M. 1982. Hybrids between rat lymphoma and mouse T cells with inducible cytolytic activity. Nature (Lond.) 298, 170.

    Article  Google Scholar 

  9. Widmer, M.B. and Bach, F.H. 1981. Antigen-driven helper cell-independent cloned cytolytic T lymphocytes. Nature (Lond.) 294:750.

    Article  CAS  Google Scholar 

  10. Kaufmann, Y., Berke, G. and Eshhar, Z. 1981. Cytotoxic T lymphocyte hybridomas that mediate specific tumor-cell lysis in vitro. Proc. Natl. Acad. Sci. USA 78:2502.

    Article  CAS  Google Scholar 

  11. Kaufmann, Y. and Berke, G. 1983. Monoclonal cytotoxic T lymphocyte-hybridomas capable of specific killing activity, antigenic responsiveness and inducible interleukin (s) secretion. J. Immunol 131:50.

    CAS  PubMed  Google Scholar 

  12. Walker, C.M., Rawls, W. RE., and Rosenthal, K. L. 1984. Generation of memory cell-mediated immune response after secondary infection of mice with pichinde virus. J. Immunol. 132:469.

    CAS  PubMed  Google Scholar 

  13. Robb, R. J., Kutny, R.M., and Chowdhry, V. 1983. Purification and partial sequence analysis of human T cell growth factor. Proc. Natl. Acad. Sci. USA 80:5990.

    Article  CAS  Google Scholar 

  14. Raulet, D. H. and Bevan, M.J. 1982. A differentiation factor required for the expression of cytotoxic T cell function. Nature (Lond.) 296:754.

    Article  CAS  Google Scholar 

  15. Wagner, H., Hardt, C., Rouse, B.T., Rollinghoff, M., Scherich, P. and Pfizenmaier, K. 1982. Dissociation of the proliferative and differential signals controlling murine cytotoxic T lymphocyte responses. J. Exp. Med. 155: 1876.

    Article  CAS  Google Scholar 

  16. Finke, H. J., Scott, J., Gillis, S., and Hilfiker, M.L. 1983. Generation of alloreactive cytotoxic T lymphocytes. Evidence for a differentiation factor distinct from IL-2. J. Immunol. 130:763.

    CAS  PubMed  Google Scholar 

  17. Robb, R.J., Munck, A. and Snith, K.A. 1981. T cell growth factor receptors. Quantitation, specificity and biological relevance. J. Exp. Med. 165: 1455.

    Article  Google Scholar 

  18. Robb, R.J. and Lin, Y. 1983. T cell growth factor: purification, interaction with the cellular receptor and in vitro synthesis. In: Thymic Hormones and Lymphokines, Goldstein, A.L., ed., Plenum Press, New York, in press.

    Google Scholar 

  19. Conzelman, A., Silva, A., Cianfriglia, M., Tougne, C., Sekaly, R. P. and Nabholz, M. 1982. Correlated expression of TCGF dependence, sensitivity to Vicia villosa lectin, and cytolytic activity in hybrids between cytolytic T cells and T lymphomas. J. Exp. Med. 156: 1335.

    Article  Google Scholar 

  20. Davignon, D., Martz, E., Reynolds, T., Kurzinger, K. and Springer, T.A. 1981. Lymphocyte function-associated antigen one (LFA-1): A surface antigen distinct from Lyt-2/3 that participates in T lymphocyte-mediated killing. Proc. Natl. Acad. Sci. USA 78:4535.

    Article  CAS  Google Scholar 

  21. Pierres, M., Goridis, C. and Golstein, P. 1982. Inhibition of murine T cell-mediated cytolysis and T cell proliferation by a rat monoclonal antibody immunoprecipitating two lymphoid cell surface polypeptides of 94,000 and 180,000 molecular weight. Eur. J. Immunol. 12:60.

    Article  CAS  Google Scholar 

  22. Bunjes, D., Hardt, C., Rollinghoff, H. and Wagner, H. 1981. Cyclosporin A mediates immunosuppression of primary cytotoxic T cell responses by impairing the release of Interleukin 1 and Interleukin 2. Eur. J. Immunol. 11:657.

    Article  CAS  Google Scholar 

  23. Palacios, R. 1981. Cyclosporin A inhibits the proliferative response and the generation of helper, suppressor and cytotoxic T cell functions in the autologous mixed lymphocyte reaction. Cell. Immunol. 61:453.

    Article  CAS  Google Scholar 

  24. Orosz, C.C., Fidelus, R.K., Roopenian, D.C., Widmer, M.B., Ferguson, R.M. and Bach, F.H. 1982. Analysis of cloned T cell function, I. Dissection of cloned T cell proliferative responses using Cyclosporin A. J.. Immunol. 129: 1865.

    CAS  PubMed  Google Scholar 

  25. Wang, B., Heacock, E., Collins, K., Hutchinson, I., Tilney, N. and Mannick, J. 1981. Suppressive effects of Cyclosporin A on the induction of alloreactivity in vitro and in vivo. J. Immunol. 127:89.

    CAS  PubMed  Google Scholar 

  26. Kaufmann, Y., Golstein, P., Pierres, M., Springer, T.A. and Eshhar, Z. 1982. LFA-1 but not Lyt-2 is associated with killing activity of cytotoxic T lymphocyte hybridomas. Nature (Lond.) 300:357.

    Article  CAS  Google Scholar 

  27. Berke, G., Gabison, D. and Feldman, M. 1975. The frequency of effector cells in populations containing cytotoxic T lymphocytes. Eur. J. Immunol. 5:813.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cell Biology, The Weizmann Institute of Science, 76100, Rehovot, Israel

    Y. Kaufmann, M. Moscovitch & G. Berke

  2. Glenolden Laboratory, E. I. duPont deNemours and Co., 19036, Glenolden, PA, USA

    R. J. Robb

  3. Surgery Branch, National Cancer Institute, 20205, Bethesda, MD, USA

    S. A. Rosenberg

Authors
  1. Y. Kaufmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Moscovitch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. J. Robb
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. A. Rosenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Berke
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. National Institutes of Health, Bethesda, Maryland, USA

    Pierre Henkart

  2. University of Massachusetts, Amherst, Massachusetts, USA

    Eric Martz

Rights and permissions

Reprints and permissions

Copyright information

© 1985 Plenum Press, New York

About this chapter

Cite this chapter

Kaufmann, Y., Moscovitch, M., Robb, R.J., Rosenberg, S.A., Berke, G. (1985). Antigen/Mitogen Induced Cytolytic Activity and IL-2 Secretion in Memory-Like CTL-Hybridomas. In: Henkart, P., Martz, E. (eds) Mechanisms of Cell-Mediated Cytotoxicity II. Advances in Experimental Medicine and Biology, vol 184. Springer, New York, NY. https://doi.org/10.1007/978-1-4684-8326-0_35

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-8326-0_35

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4684-8328-4

  • Online ISBN: 978-1-4684-8326-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation