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. 1986 Mar;83(6):1886–1890. doi: 10.1073/pnas.83.6.1886

Autocrine growth inhibition of a cloned line of helper T cells.

J B Horowitz, J Kaye, P J Conrad, M E Katz, C A Janeway Jr
PMCID: PMC323189  PMID: 2937064

Abstract

The growth of T lymphocytes is dependent on the T-cell growth factor interleukin 2 (IL-2), which causes T cells bearing high-affinity receptors for IL-2 to proliferate. Most cloned helper-T-cell lines can be shown to both produce and respond to IL-2; thus, growth of such cells is by an autocrine mechanism. We report that the failure of the cloned murine T-cell line D10.G4.1 to respond to its own IL-2 results from the secretion, by the same cells, of a potent inhibitor of the IL-2-driven T-cell proliferative response. This inhibition can be overcome by increasing the number of IL-2 receptors expressed by the target cell. In the cloned T-cell line producing the inhibitory substance, this increase in IL-2 receptors is driven by the monokine interleukin-1. We propose that this inhibitor of IL-2 responses may play a role in preventing "bystander" activation of T cells by IL-2 released in vivo and could be a potent pharmacologic agent.

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Selected References

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

  1. Auron P. E., Webb A. C., Rosenwasser L. J., Mucci S. F., Rich A., Wolff S. M., Dinarello C. A. Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7907–7911. doi: 10.1073/pnas.81.24.7907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cantrell D. A., Smith K. A. Transient expression of interleukin 2 receptors. Consequences for T cell growth. J Exp Med. 1983 Dec 1;158(6):1895–1911. doi: 10.1084/jem.158.6.1895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Conrad P. J., Janeway C. A., Jr The expression of I-Ed molecules in F1 hybrid mice detected with antigen-specific, I-Ed-restricted cloned T-cell lines. Immunogenetics. 1984;20(3):311–319. doi: 10.1007/BF00364212. [DOI] [PubMed] [Google Scholar]
  4. Jegasothy B. V., Battles D. R. Immuno-suppressive lymphocyte factors-III. Complete purification and partial characterization of human inhibitor of DNA synthesis. Mol Immunol. 1981 May;18(5):395–401. doi: 10.1016/0161-5890(81)90101-2. [DOI] [PubMed] [Google Scholar]
  5. Jegasothy B. V., Battles D. R. Immuno-suppressive lymphocyte factors. I. Purification of inhibitor of DNA synthesis to homogeneity. J Exp Med. 1979 Sep 19;150(3):622–632. doi: 10.1084/jem.150.3.622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kaye J., Gillis S., Mizel S. B., Shevach E. M., Malek T. R., Dinarello C. A., Lachman L. B., Janeway C. A., 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. 1984 Sep;133(3):1339–1345. [PubMed] [Google Scholar]
  7. Kaye J., Janeway C. A., Jr Induction of receptors for interleukin 2 requires T cell Ag:Ia receptor crosslinking and interleukin 1. Lymphokine Res. 1984 Summer;3(4):175–182. [PubMed] [Google Scholar]
  8. Kaye J., Janeway C. A., Jr The Fab fragment of a directly activating monoclonal antibody that precipitates a disulfide-linked heterodimer from a helper T cell clone blocks activation by either allogeneic Ia or antigen and self-Ia. J Exp Med. 1984 May 1;159(5):1397–1412. doi: 10.1084/jem.159.5.1397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kaye J., Jones B., Janeway C. A., Jr The structure and function of T cell receptor complexes. Immunol Rev. 1984 Oct;81:39–63. doi: 10.1111/j.1600-065x.1984.tb01104.x. [DOI] [PubMed] [Google Scholar]
  10. Kaye J., Porcelli S., Tite J., Jones B., Janeway C. A., Jr Both a monoclonal antibody and antisera specific for determinants unique to individual cloned helper T cell lines can substitute for antigen and antigen-presenting cells in the activation of T cells. J Exp Med. 1983 Sep 1;158(3):836–856. doi: 10.1084/jem.158.3.836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kurt-Jones E. A., Beller D. I., Mizel S. B., Unanue E. R. Identification of a membrane-associated interleukin 1 in macrophages. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1204–1208. doi: 10.1073/pnas.82.4.1204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mills B. J., Mitsky P. S., Todd C. W. Acid treatment enhances IL-2 activity of conditioned medium. J Immunol Methods. 1984 Feb 24;67(1):73–78. doi: 10.1016/0022-1759(84)90086-3. [DOI] [PubMed] [Google Scholar]
  13. Ruddle N. H. Delayed hypersensitivity to soluble antigens in mice. II. Analysis in vitro. Int Arch Allergy Appl Immunol. 1979;58(1):44–52. doi: 10.1159/000232172. [DOI] [PubMed] [Google Scholar]
  14. Smith K. A. Interleukin 2. Annu Rev Immunol. 1984;2:319–333. doi: 10.1146/annurev.iy.02.040184.001535. [DOI] [PubMed] [Google Scholar]
  15. Sporn M. B., Roberts A. B. Autocrine growth factors and cancer. 1985 Feb 28-Mar 6Nature. 313(6005):745–747. doi: 10.1038/313745a0. [DOI] [PubMed] [Google Scholar]
  16. Stone-Wolff D. S., Yip Y. K., Kelker H. C., Le J., Henriksen-Destefano D., Rubin B. Y., Rinderknecht E., Aggarwal B. B., Vilcek J. Interrelationships of human interferon-gamma with lymphotoxin and monocyte cytotoxin. J Exp Med. 1984 Mar 1;159(3):828–843. doi: 10.1084/jem.159.3.828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Taniguchi T., Matsui H., Fujita T., Takaoka C., Kashima N., Yoshimoto R., Hamuro J. Structure and expression of a cloned cDNA for human interleukin-2. Nature. 1983 Mar 24;302(5906):305–310. doi: 10.1038/302305a0. [DOI] [PubMed] [Google Scholar]
  18. Tite J. P., Janeway C. A., Jr Antigen-dependent selection of B lymphoma cells varying in Ia density by cloned antigen-specific L3T4a+ T cells: a possible in vitro model for B cell adaptive differentiation. J Mol Cell Immunol. 1984;1(4):253–265. [PubMed] [Google Scholar]
  19. Tite J. P., Janeway C. A., Jr Cloned helper T cells can kill B lymphoma cells in the presence of specific antigen: Ia restriction and cognate vs. noncognate interactions in cytolysis. Eur J Immunol. 1984 Oct;14(10):878–886. doi: 10.1002/eji.1830141004. [DOI] [PubMed] [Google Scholar]
  20. Tite J. P., Powell M. B., Ruddle N. H. Protein-antigen specific Ia-restricted cytolytic T cells: analysis of frequency, target cell susceptibility, and mechanism of cytolysis. J Immunol. 1985 Jul;135(1):25–33. [PubMed] [Google Scholar]

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