Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1989 Aug;67(4):484–488.

Cyclic adenosine 3',5'-monophosphate metabolism in activated T-cell clones.

D Oksenberg 1, J R Oksenberg 1, K Sakai 1, S J Peroutka 1, L Steinman 1
PMCID: PMC1385318  PMID: 2475434

Abstract

The role of cAMP in lymphocyte proliferation was investigated in the response of a monoclonal T-cell population to a specific antigen and compared to the response to interleukin-2 (IL-2) and allogeneic cells. Myelin basic protein (MBP)-reactive and encephalitogenic T-cell clones were established from long-term lines derived from SJL/J (H-2s) mice. The clone 4b.14a recognizes the peptide sequence 89-101 of the MBP molecule in association with 1-As products of the major histocompatibility complex (MHC). Incubation of 4b.14a cells with syngeneic antigen-presenting cells, previously pulsed with the 89-101 synthetic peptide or with 80 U/ml of IL-2, or allogeneic H-2Ik cells, resulted in a significant increase in the accumulation of intracellular cAMP. This increase was preceded by a peak in membranal adenylate cyclase (AC) activity. Parallel time kinetics but significantly higher cAMP production and AC activity were observed when the cells were treated with pertussis toxin. At the same concentrations the toxin inhibits cellular proliferative responses, assayed by [3H]thymidine incorporation. Our results indicate the involvement of cAMP as a positive signal in the activation of the 4b.14a clone.

Full text

PDF
484

Selected References

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

  1. Beckner S. K., Farrar W. L. Interleukin 2 modulation of adenylate cyclase. Potential role of protein kinase C. J Biol Chem. 1986 Mar 5;261(7):3043–3047. [PubMed] [Google Scholar]
  2. Cambier J. C., Justement L. B., Newell M. K., Chen Z. Z., Harris L. K., Sandoval V. M., Klemsz M. J., Ransom J. T. Transmembrane signals and intracellular "second messengers" in the regulation of quiescent B-lymphocyte activation. Immunol Rev. 1987 Feb;95:37–57. doi: 10.1111/j.1600-065x.1987.tb00499.x. [DOI] [PubMed] [Google Scholar]
  3. Freundlich B., Avdalovic N. Use of gelatin/plasma coated flasks for isolating human peripheral blood monocytes. J Immunol Methods. 1983 Aug 12;62(1):31–37. doi: 10.1016/0022-1759(83)90107-2. [DOI] [PubMed] [Google Scholar]
  4. Gilman A. G. A protein binding assay for adenosine 3':5'-cyclic monophosphate. Proc Natl Acad Sci U S A. 1970 Sep;67(1):305–312. doi: 10.1073/pnas.67.1.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Imboden J. B., Shoback D. M., Pattison G., Stobo J. D. Cholera toxin inhibits the T-cell antigen receptor-mediated increases in inositol trisphosphate and cytoplasmic free calcium. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5673–5677. doi: 10.1073/pnas.83.15.5673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Imboden J. B., Stobo J. D. Transmembrane signalling by the T cell antigen receptor. Perturbation of the T3-antigen receptor complex generates inositol phosphates and releases calcium ions from intracellular stores. J Exp Med. 1985 Mar 1;161(3):446–456. doi: 10.1084/jem.161.3.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  8. Letterio J. J., Coughlin S. R., Williams L. T. Pertussis toxin-sensitive pathway in the stimulation of c-myc expression and DNA synthesis by bombesin. Science. 1986 Nov 28;234(4780):1117–1119. doi: 10.1126/science.3465038. [DOI] [PubMed] [Google Scholar]
  9. Millis A. J., Forrest G. A., Pious D. A. Cyclic AMP dependent regulation of mitosis in human lymphoid cells. Exp Cell Res. 1974 Feb;83(2):335–343. doi: 10.1016/0014-4827(74)90347-4. [DOI] [PubMed] [Google Scholar]
  10. Morse J. H., Kong A. S., Lindenbaum J., Morse S. I. The mitogenic effect of the lymphocytosis promoting factor from Bordetella pertussis on human lymphocytes. J Clin Invest. 1977 Sep;60(3):683–692. doi: 10.1172/JCI108820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Nel A. E., Vandenplas M., Wooten M. M., Cooper R., Vandenplas S., Rheeder A., Daniels J. Cholera toxin partially inhibits the T-cell response to phytohaemagglutinin through the ADP-ribosylation of a 45 kDa membrane protein. Biochem J. 1988 Dec 1;256(2):383–390. doi: 10.1042/bj2560383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Nel A. E., Wooten M. W., Galbraith R. M. Molecular signaling mechanisms in T-lymphocyte activation pathways: a review and future prospects. Clin Immunol Immunopathol. 1987 Aug;44(2):167–186. doi: 10.1016/0090-1229(87)90064-x. [DOI] [PubMed] [Google Scholar]
  13. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  14. Oettgen H. C., Terhorst C., Cantley L. C., Rosoff P. M. Stimulation of the T3-T cell receptor complex induces a membrane-potential-sensitive calcium influx. Cell. 1985 Mar;40(3):583–590. doi: 10.1016/0092-8674(85)90206-5. [DOI] [PubMed] [Google Scholar]
  15. Pastan I. H., Johnson G. S., Anderson W. B. Role of cyclic nucleotides in growth control. Annu Rev Biochem. 1975;44:491–522. doi: 10.1146/annurev.bi.44.070175.002423. [DOI] [PubMed] [Google Scholar]
  16. Rechler M. M., Bruni C. B., Podskalny J. M., Warner W., Carchman R. A. Modulation of serum-stimulated DNA synthesis in cultured human fibroblasts by cAMP. Exp Cell Res. 1977 Feb;104(2):411–422. doi: 10.1016/0014-4827(77)90106-9. [DOI] [PubMed] [Google Scholar]
  17. Rozengurt E. Early signals in the mitogenic response. Science. 1986 Oct 10;234(4773):161–166. doi: 10.1126/science.3018928. [DOI] [PubMed] [Google Scholar]
  18. Rozengurt E., Mendoza S. A. Synergistic signals in mitogenesis: role of ion fluxes, cyclic nucleotides and protein kinase C in Swiss 3T3 cells. J Cell Sci Suppl. 1985;3:229–242. doi: 10.1242/jcs.1985.supplement_3.20. [DOI] [PubMed] [Google Scholar]
  19. Sakai K., Sinha A. A., Mitchell D. J., Zamvil S. S., Rothbard J. B., McDevitt H. O., Steinman L. Involvement of distinct murine T-cell receptors in the autoimmune encephalitogenic response to nested epitopes of myelin basic protein. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8608–8612. doi: 10.1073/pnas.85.22.8608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sakai K., Zamvil S. S., Mitchell D. J., Lim M., Rothbard J. B., Steinman L. Characterization of a major encephalitogenic T cell epitope in SJL/J mice with synthetic oligopeptides of myelin basic protein. J Neuroimmunol. 1988 Aug;19(1-2):21–32. doi: 10.1016/0165-5728(88)90032-x. [DOI] [PubMed] [Google Scholar]
  21. Salomon Y. Adenylate cyclase assay. Adv Cyclic Nucleotide Res. 1979;10:35–55. [PubMed] [Google Scholar]
  22. Shenker B. J., Matt W. C. Suppression of human lymphocyte responsiveness by forskolin: reversal by 12-O-tetradecanoyl phorbol 13-acetate, diacylglycerol and ionomycin. Immunopharmacology. 1987 Feb;13(1):73–86. doi: 10.1016/0162-3109(87)90028-2. [DOI] [PubMed] [Google Scholar]
  23. Wang T., Sheppard J. R., Foker J. E. Rise and fall of cyclic AMP required for onset of lymphocyte DNA synthesis. Science. 1978 Jul 14;201(4351):155–157. doi: 10.1126/science.208147. [DOI] [PubMed] [Google Scholar]
  24. Watson J. The involvement of cyclic nucleotide metabolism in the initiation of lymphocyte proliferation induced by mitogens. J Immunol. 1976 Nov;117(5 Pt 1):1656–1663. [PubMed] [Google Scholar]
  25. Zeilig C. E., Goldberg N. D. Cell-cycle-related changes of 3':5'-cyclic GMP levels in Novikoff hepatoma cells. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1052–1056. doi: 10.1073/pnas.74.3.1052. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES