Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1986 Jul;78(1):214–220. doi: 10.1172/JCI112554

Proliferative signals for suppressor T cells. Helper cells stimulated with pokeweed mitogen in vitro produce a suppressor cell growth factor.

E J Fox, R G Cook, D E Lewis, R R Rich
PMCID: PMC329552  PMID: 2941453

Abstract

To define molecular signals elaborated by inducer populations supporting growth or differentiation of T8+ cells, we collected supernatants of pokeweed mitogen (PWM)-stimulated cultures depleted of T8+ cells. When added to purified T8+ cells, these supernatants caused significant proliferation. PWM plus interleukin 2 (IL-2) in amounts equivalent to those in the supernatant could not reconstitute the response caused by the supernatant. T8+ cells activated by supernatants obtained from PWM-pulsed T4+ cells suppressed fresh PWM cultures. Although exhibiting little proliferation, T8+ cells cultured for 6 d in PWM plus IL-2 still suppressed a fresh PWM response. The supernatants therefore contain an additional T suppressor cell growth factor (TsGF). Elaboration of TsGF required radiosensitive T4+Leu8+ cells. Molecular weight determination by high performance liquid chromatography gave a single peak of TsGF activity at approximately 8,000. Finally, whereas TsGF in the absence of IL-2 could not support the proliferation of T suppressor cells, it did cause T8+ cells to become strongly IL-2 receptor-positive.

Full text

PDF
214

Selected References

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

  1. Bensussan A., Acuto O., Hussey R. E., Milanese C., Reinherz E. L. T3-Ti receptor triggering of T8+ suppressor T cells leads to unresponsiveness to interleukin-2. Nature. 1984 Oct 11;311(5986):565–567. doi: 10.1038/311565a0. [DOI] [PubMed] [Google Scholar]
  2. Brown M. F., Van M., Abramson S. L., Fox E. J., Rich R. R. Cellular requirements for induction of human primary proliferative responses to trinitrophenyl-modified cells. J Immunol. 1984 Jan;132(1):19–24. [PubMed] [Google Scholar]
  3. 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]
  4. Chen T. R. In situ detection of mycoplasma contamination in cell cultures by fluorescent Hoechst 33258 stain. Exp Cell Res. 1977 Feb;104(2):255–262. doi: 10.1016/0014-4827(77)90089-1. [DOI] [PubMed] [Google Scholar]
  5. Damle N. K., Mohagheghpour N., Engleman E. G. Activation of antigen-specific suppressor T lymphocytes in man involves dual recognition of self class I MHC molecules and Leu-4/T3-associated structures on the surface of inducer T lymphocytes. J Immunol. 1984 Sep;133(3):1235–1240. [PubMed] [Google Scholar]
  6. Depper J. M., Leonard W. J., Drogula C., Krönke M., Waldmann T. A., Greene W. C. Interleukin 2 (IL-2) augments transcription of the IL-2 receptor gene. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4230–4234. doi: 10.1073/pnas.82.12.4230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dinarello C. A., Clowes G. H., Jr, Gordon A. H., Saravis C. A., Wolff S. M. Cleavage of human interleukin 1: isolation of a peptide fragment from plasma of febrile humans and activated monocytes. J Immunol. 1984 Sep;133(3):1332–1338. [PubMed] [Google Scholar]
  8. Erard F., Corthesy P., Nabholz M., Lowenthal J. W., Zaech P., Plaetinck G., MacDonald H. R. Interleukin 2 is both necessary and sufficient for the growth and differentiation of lectin-stimulated cytolytic T lymphocyte precursors. J Immunol. 1985 Mar;134(3):1644–1652. [PubMed] [Google Scholar]
  9. Gillis S., Mochizuki D. Y., Conlon P. J., Hefeneider S. H., Ramthun C. A., Gillis A. E., Frank M. B., Henney C. S., Watson J. D. Molecular characterization of interleukin 2. Immunol Rev. 1982;63:167–209. doi: 10.1111/j.1600-065x.1982.tb00415.x. [DOI] [PubMed] [Google Scholar]
  10. Howard M., Nakanishi K., Paul W. E. B cell growth and differentiation factors. Immunol Rev. 1984 Apr;78:185–210. doi: 10.1111/j.1600-065x.1984.tb00482.x. [DOI] [PubMed] [Google Scholar]
  11. Inouye H., Hank J. A., Alter B. J., Bach F. H. TCGF production for cloning and growth of functional human T lymphocytes. Scand J Immunol. 1980;12(2):149–154. doi: 10.1111/j.1365-3083.1980.tb00051.x. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Lachman L. B., Shih L. C., Brown D. C. Interleukin 1 from human leukemic monocytes. Methods Enzymol. 1985;116:467–479. doi: 10.1016/s0076-6879(85)16038-6. [DOI] [PubMed] [Google Scholar]
  14. Mizel S. B. Interleukin 1 and T cell activation. Immunol Rev. 1982;63:51–72. doi: 10.1111/j.1600-065x.1982.tb00411.x. [DOI] [PubMed] [Google Scholar]
  15. Mohagheghpour N., Benike C. J., Kansas G., Bieber C., Engleman E. G. Activation of antigen-specific suppressor T cells in the presence of cyclosporin requires interactions between T cells of inducer and suppressor lineage. J Clin Invest. 1983 Dec;72(6):2092–2100. doi: 10.1172/JCI111174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Puck J. M., Rich R. R. Regulatory interactions governing the proliferation of T cell subsets stimulated with pokeweed mitogen. J Immunol. 1984 Mar;132(3):1106–1112. [PubMed] [Google Scholar]
  17. Reinherz E. L., Kung P. C., Goldstein G., Levey R. H., Schlossman S. F. Discrete stages of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T-cell lineage. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1588–1592. doi: 10.1073/pnas.77.3.1588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rich R. R., Rich S. S. T-T cell interactions in cell-mediated immune responses to major histocompatibility complex antigens. Crit Rev Immunol. 1983;4(2):129–168. [PubMed] [Google Scholar]
  19. Robb R. J., Kutny R. M., Chowdhry V. Purification and partial sequence analysis of human T-cell growth factor. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5990–5994. doi: 10.1073/pnas.80.19.5990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rosenberg S. A., Lipsky P. E. Monocyte dependence of pokeweed mitogen-induced differentiation of immunoglobulin-secreting cells from human peripheral blood mononuclear cells. J Immunol. 1979 Mar;122(3):926–931. [PubMed] [Google Scholar]
  21. Smith K. A., Favata M. F., Oroszlan S. Production and characterization of monoclonal antibodies to human interleukin 2: strategy and tactics. J Immunol. 1983 Oct;131(4):1808–1815. [PubMed] [Google Scholar]
  22. Smith K. A. T-cell growth factor. Immunol Rev. 1980;51:337–357. doi: 10.1111/j.1600-065x.1980.tb00327.x. [DOI] [PubMed] [Google Scholar]
  23. Thomas Y., Sosman J., Irigoyen O., Friedman S. M., Kung P. C., Goldstein G., Chess L. Functional analysis of human T cell subsets defined by monoclonal antibodies. I. Collaborative T-T interactions in the immunoregulation of B cell differentiation. J Immunol. 1980 Dec;125(6):2402–2408. [PubMed] [Google Scholar]
  24. Tilles J. G., Finland M. Microassay for human and chick cell interferons. Appl Microbiol. 1968 Nov;16(11):1706–1707. doi: 10.1128/am.16.11.1706-1707.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Watson J. Continuous proliferation of murine antigen-specific helper T lymphocytes in culture. J Exp Med. 1979 Dec 1;150(6):1510–1519. doi: 10.1084/jem.150.6.1510. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES