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. 1984 Feb 1;159(2):647–652. doi: 10.1084/jem.159.2.647

Cytotoxic T cells both produce and respond to interleukin 2

L Andrus, A Granelli-Piperno, E Reich
PMCID: PMC2187234  PMID: 6607316

Abstract

Interleukin 2 (IL-2) is a T cell-derived lymphokine that serves as a cofactor for the in vitro response of T lymphocytes to antigen and plays an important role in regulating the growth and/or differentiation of these cells (1, 2). It has been postulated (2, 3) that IL-2 is produced by a discrete regulatory T cell subset, with its effects being exerted on a second, functionally distinct subpopulation of T cells. Cytotoxic T cells have been included in the IL-2-responsive subset (3). Several models of immune regulation have further assumed that the T lymphocyte pool is divided into a complex array of genetically preprogrammed T cell subtypes, each performing a specific regulatory or effector function (4, 5). However, recent results from several laboratories (6-8) have failed to support such a strict functional subdivision of the T cell pool. The availability of highly purified mouse IL-2 (1) prompted us to reevaluate the distinction, if any, between IL-2-producing and IL-2- responsive T cells. For this purpose, we resorted to a cell-cloning procedure using activated T lymphocytes that were maintained only for short periods in culture. T cell clones were tested for cytotoxic activity, responsiveness to IL-2, and for the capacity to produce IL-2 after appropriate stimulation. We found no evidence for the existence of a major functional subdivision involving these parameters among alloantigen-activated T cells: the majority of clones analyzed could perform all three functions.

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Selected References

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

  1. Andrus L., Lafferty K. J. Interleukin 2 production by alloantigen (H-2) activated T cells. Aust J Exp Biol Med Sci. 1981 Aug;59(4):413–426. doi: 10.1038/icb.1981.35. [DOI] [PubMed] [Google Scholar]
  2. Braciale T. J., Andrew M. E., Braciale V. L. Heterogeneity and specificity of cloned lines of influenza-virus specific cytotoxic T lymphocytes. J Exp Med. 1981 Apr 1;153(4):910–923. doi: 10.1084/jem.153.4.910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cantor H., Boyse E. A. Functional subclasses of T-lymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a differentiative process independent of antigen. J Exp Med. 1975 Jun 1;141(6):1376–1389. doi: 10.1084/jem.141.6.1376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Clark-Lewis I., Schrader J. W. Biochemical characterization of regulatory factors derived from T cell hybridomas and spleen cells. I. Separation of T cell growth factor and T cell replacing factor from granulocyte-macrophage colony-stimulating factor. J Immunol. 1982 Jan;128(1):168–174. [PubMed] [Google Scholar]
  5. DUNN T. B., POTTER M. A transplantable mast-cell neoplasm in the mouse. J Natl Cancer Inst. 1957 Apr;18(4):587–601. [PubMed] [Google Scholar]
  6. Dennert G., Weiss S., Warner J. F. T cells may express multiple activities: specific allohelp, cytolysis, and delayed-type hypersensitivity are expressed by a cloned T-cell line. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4540–4543. doi: 10.1073/pnas.78.7.4540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gillis S., Crabtree G. R., Smith K. A. Glucocorticoid-induced inhibition of T cell growth factor production. I. The effect on mitogen-induced lymphocyte proliferation. J Immunol. 1979 Oct;123(4):1624–1631. [PubMed] [Google Scholar]
  8. Glasebrook A. L., Fitch F. W. Alloreactive cloned T cell lines. I. Interactions between cloned amplifier and cytolytic T cell lines. J Exp Med. 1980 Apr 1;151(4):876–895. doi: 10.1084/jem.151.4.876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Granelli-Piperno A., Vassalli J. D., Reich E. Purification of murine T cell growth factor. A lymphocyte mitogen with helper activity. J Exp Med. 1981 Aug 1;154(2):422–431. doi: 10.1084/jem.154.2.422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kelso A., Macdonald H. R. Precursor frequency analysis of lymphokine-secreting alloreactive T lymphocytes. Dissociation of subsets producing interleukin 2, macrophage-activating factor, and granulocyte-macrophage colony-stimulating factor on the basis of Lyt-2 phenotype. J Exp Med. 1982 Nov 1;156(5):1366–1379. doi: 10.1084/jem.156.5.1366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lafferty K. J., Bootes A., Dart G., Talmage D. W. Effect of organ culture on the survival of thyroid allografts in mice. Transplantation. 1976 Aug;22(2):138–149. doi: 10.1097/00007890-197608000-00009. [DOI] [PubMed] [Google Scholar]
  12. Lafferty K. J., Prowse S. J., Al-Adra A., Warren H. S., Vasalli J., Reich E. An improved assay for interleukin 2 (lymphocyte growth factor) produced by mitogen-activated lymphocytes. Aust J Exp Biol Med Sci. 1980 Dec;58(6):533–544. doi: 10.1038/icb.1980.55. [DOI] [PubMed] [Google Scholar]
  13. Okada M., Henney C. S. The differentiation of cytotoxic T cells in vitro. II. Amplifying factor(s) produced in primary mixed lymphocyte cultures against K/D stimuli require the presence of Lyt 2+ cells but not Lyt 1+ cells. J Immunol. 1980 Jul;125(1):300–307. [PubMed] [Google Scholar]
  14. Schreier M. H., Iscove N. N., Tees R., Aarden L., von Boehmer H. Clones of killer and helper T cells: growth requirements, specificity and retention of function in long-term culture. Immunol Rev. 1980;51:315–336. doi: 10.1111/j.1600-065x.1980.tb00326.x. [DOI] [PubMed] [Google Scholar]
  15. Wagner H., Räollinghoff M., Pfizenmaier K., Hardt C., Johnscher G. T-T cell interactions during in vitro cytotoxic T lymphocyte (CTL) responses. II. Helper factor from activated Lyt 1+ T cells is rate limiting i) in T cell responses to nonimmunogenic alloantigen, ii) in thymocyte responses to allogeneic stimulator cells, and III) recruits allo- or H-2-restricted CTL precursors from the Lyt 123+ T subset. J Immunol. 1980 Mar;124(3):1058–1067. [PubMed] [Google Scholar]
  16. Wagner H., Röllinghoff M. T-T-cell interactions during the vitro cytotoxic allograft responses. I. Soluble products from activated Lyl+ T cells trigger autonomously antigen-primed Ly23+ T cells to cell proliferation and cytolytic activity. J Exp Med. 1978 Dec 1;148(6):1523–1538. doi: 10.1084/jem.148.6.1523. [DOI] [PMC free article] [PubMed] [Google Scholar]

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