Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1981 Feb;78(2):1133–1137. doi: 10.1073/pnas.78.2.1133

T-Cell lymphoma model for the analysis of interleukin 1-mediated T-cell activation.

S Gillis, S B Mizel
PMCID: PMC319961  PMID: 6785748

Abstract

Several laboratories have recently demonstrated that the requirement for macrophages in mitogen-induced production of murine T-cell interleukin 2 (IL-2; formerly referred to as "T-cell growth factor") could be circumvented by using the macrophage-derived peptide interleukin 1 (IL-1; formerly referred to as "lymphocyte-activating factor"). Using two cloned T-cell lymphomas, we investigated the mechanism through which IL-1 exerted its effect on IL-2 production. One of the cell lines used (LBRM-33 5A4) produces large concentrations of IL-2 upon mitogen stimulation, whereas the second (LBRM-33 1A5) is incapable of producing IL-2 in response to mitogen. It was observed that addition of purified IL-1 to nonproducer 1A5 cells converted them to a state in which subsequent mitogen stimulation triggered production of IL-2. The concentration of IL-2 produced by IL-1 treated 1A5 cells was equivalent in magnitude to that generated by mitogen-stimulated 5A4 cells (500-1000 units/ml, or approximately 1000 times the concentration of IL-2 contained in conventional preparations of murine mitogen-conditioned medium). The observations that (i) brief exposure to IL-1 was sufficient for 1A5 cell conversion to IL-2 production and (ii) IL-1 could actively be absorbed from culture medium by live or fixed 1A5 cells led us to propose the existence of IL-1 receptors on responsive 1A5 cells. On the basis of these experiments, we have postulated that IL-1 mediates its effect on immune reactivity (enhancement of thymocyte mitogenesis and induction of antibody and cytotoxic T cell responses) by maturation of a subset of immature T cells to the point where they are capable of IL-2 production. Subsequent release of IL-2 after ligand activation allows for clonal expansion of activated T cells which mediate particular effector functions.

Full text

PDF
1133

Selected References

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

  1. Farrar J. J., Mizel S. B., Fuller-Farrar J., Farrar W. L., Hilfiker M. L. Macrophage-independent activation of helper T cells. I. Production of Interleukin 2. J Immunol. 1980 Aug;125(2):793–798. [PubMed] [Google Scholar]
  2. Farrar J. J., Simon P. L., Koopman W. J., Fuller-Bonar J. Biochemical relationship of thymocyte mitogenic factor and factors enhancing humoral and cell-mediated immune responses. J Immunol. 1978 Oct;121(4):1353–1360. [PubMed] [Google Scholar]
  3. Gillis S., Baker P. E., Ruscetti F. W., Smith K. A. Long-term culture of human antigen-specific cytotoxic T-cell lines. J Exp Med. 1978 Oct 1;148(4):1093–1098. doi: 10.1084/jem.148.4.1093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
  5. Gillis S., Scheid M., Watson J. Biochemical and biologic characterization of lymphocyte regulatory molecules. III. The isolation and phenotypic characterization of Interleukin-2 producing T cell lymphomas. J Immunol. 1980 Dec;125(6):2570–2578. [PubMed] [Google Scholar]
  6. Gillis S., Smith K. A. Long term culture of tumour-specific cytotoxic T cells. Nature. 1977 Jul 14;268(5616):154–156. doi: 10.1038/268154a0. [DOI] [PubMed] [Google Scholar]
  7. Gillis S., Smith K. A., Watson J. Biochemical characterization of lymphocyte regulatory molecules. II. Purification of a class of rat and human lymphokines. J Immunol. 1980 Apr;124(4):1954–1962. [PubMed] [Google Scholar]
  8. Gillis S., Union N. A., Baker P. E., Smith K. A. The in vitro generation and sustained culture of nude mouse cytolytic T-lymphocytes. J Exp Med. 1979 Jun 1;149(6):1460–1476. doi: 10.1084/jem.149.6.1460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Koopman W. J., Farrar J. J., Fuller-Bonar J. Evidence for the identification of lymphocyte activating factor as the adherent cell-derived mediator responsible for enhanced antibody synthesis by nude mouse spleen cells. Cell Immunol. 1978 Jan;35(1):92–98. doi: 10.1016/0008-8749(78)90129-6. [DOI] [PubMed] [Google Scholar]
  10. Larsson E. L., Iscove N. N., Coutinho A. Two distinct factors are required for induction of T-cell growth. Nature. 1980 Feb 14;283(5748):664–666. doi: 10.1038/283664a0. [DOI] [PubMed] [Google Scholar]
  11. Mastro A. M., Mueller G. C. Synergistic action of phorbol esters in mitogen-activated bovine lymphocytes. Exp Cell Res. 1974 Sep;88(1):40–46. doi: 10.1016/0014-4827(74)90615-6. [DOI] [PubMed] [Google Scholar]
  12. Mizel S. B. Biochemical and biological characterization of lymphocyte-activating factor (LAF) produced by the murine macrophage cell line, P388D. Ann N Y Acad Sci. 1979;332:539–549. doi: 10.1111/j.1749-6632.1979.tb47148.x. [DOI] [PubMed] [Google Scholar]
  13. Mizel S. B., Oppenheim J. J., Rosenstreich D. L. Characterization of lymphocyte-activating factor (LAF) produced by the macrophage cell line, P388D1. I. Enhancement of LAF production by activated T lymphocytes. J Immunol. 1978 May;120(5):1497–1503. [PubMed] [Google Scholar]
  14. Mizel S. B. Studies on the purification and structure-functional relationships of murine lymphocyte activating factor (Interleukin 1). Mol Immunol. 1980 May;17(5):571–577. doi: 10.1016/0161-5890(80)90155-8. [DOI] [PubMed] [Google Scholar]
  15. Rosenstreich D. L., Mizel S. B. Signal requirements for T lymphocyte activation. I. Replacement of macrophage function with phorbol myristic acetate. J Immunol. 1979 Oct;123(4):1749–1754. [PubMed] [Google Scholar]
  16. Simon P. L., Farrar J. J., Dind P. D. Biochemical relationship between murine immune interferon and a killer cell helper factor. J Immunol. 1979 Jan;122(1):127–132. [PubMed] [Google Scholar]
  17. Smith K. A., Gillis S., Baker P. E., McKenzie D., Ruscetti F. W. T-cell growth factor-mediated T-cell proliferation. Ann N Y Acad Sci. 1979;332:423–432. doi: 10.1111/j.1749-6632.1979.tb47136.x. [DOI] [PubMed] [Google Scholar]
  18. Smith K. A., Lachman L. B., Oppenheim J. J., Favata M. F. The functional relationship of the interleukins. J Exp Med. 1980 Jun 1;151(6):1551–1556. doi: 10.1084/jem.151.6.1551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wagner H., Hardt C., Heeg K., Röllinghoff M., Pfizenmaier K. T-cell-derived helper factor allows in vivo induction of cytotoxic T cells in nu/nu mice. Nature. 1980 Mar 20;284(5753):278–278. doi: 10.1038/284278a0. [DOI] [PubMed] [Google Scholar]
  20. Watson J., Gillis S., Marbrook J., Mochizuki D., Smith K. A. Biochemical and biological characterization of lymphocyte regulatory molecules. I. Purification of a class of murine lymphokines. J Exp Med. 1979 Oct 1;150(4):849–861. doi: 10.1084/jem.150.4.849. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES