Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1977 Dec 1;146(6):1719–1734. doi: 10.1084/jem.146.6.1719

Suppression of human T-cell mitogenesis by prostaglandin. Existence of a prostaglandin-producing suppressor cell

PMCID: PMC2181914  PMID: 411876

Abstract

Small amounts of PGE inhibit mitogen-induced [3H]thymidine incorporation in human peripheral lymphocytes. The 50% inhibitory concentration is approximately 10(-7) M, and this is reduced to approximately 10(-8) M when endogenous PGE production is blocked. PGE inhibits PHA- and Con A-stimulated cultures much better than PWM cultures, suggesting a differential effect of PGE on T-cell vs. B-cell function. In vitro blockade of PG synthesis results in approximately 50% increase in [3H]thymidine incorporation in PHA cultures. PGE is produced endogenously in PHA cultures by glass adherent suppressor cells.

Full Text

The Full Text of this article is available as a PDF (955.9 KB).

Selected References

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

  1. Bankhurst A. D., Williams R. C., Jr Identification of DNA-binding lymphocytes in patients with systemic lupus erythematosus. J Clin Invest. 1975 Dec;56(6):1378–1385. doi: 10.1172/JCI108218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berenbaum M. C., Cope W. A., Bundick R. V. Synergistic effect of cortisol and prostaglandin E2 on the PHA response. Relation to immunosuppression induced by trauma. Clin Exp Immunol. 1976 Dec;26(3):534–541. [PMC free article] [PubMed] [Google Scholar]
  3. Bleich H. L., Boro E. S. Control of lymphocyte function. N Engl J Med. 1976 Nov 18;295(21):1180–1186. doi: 10.1056/NEJM197611182952110. [DOI] [PubMed] [Google Scholar]
  4. Bresnihan B., Jasin H. E. Suppressor function of peripheral blood mononuclear cells in normal individuals and in patients with systemic lupus erythematosus. J Clin Invest. 1977 Jan;59(1):106–116. doi: 10.1172/JCI108607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Broder S., Humphrey R., Durm M., Blackman M., Meade B., Goldman C., Strober W., Waldmann T. Impaired synthesis of polyclonal (non-paraprotein) immunoglobulins by circulating lymphocytes from patients with multiple myeloma Role of suppressor cells. N Engl J Med. 1975 Oct 30;293(18):887–892. doi: 10.1056/NEJM197510302931801. [DOI] [PubMed] [Google Scholar]
  6. Delespesse G., Gausset P., Cauchie C., Govaerts A. Cellular aspects of selective IgA deficiency. Clin Exp Immunol. 1976 May;24(2):273–279. [PMC free article] [PubMed] [Google Scholar]
  7. Ferraris V. A., DeRubertis F. R. Release of prostaglandin by mitogen- and antigen-stimulated leukocytes in culture. J Clin Invest. 1974 Aug;54(2):378–386. doi: 10.1172/JCI107773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Folch H., Waksman B. H. Regulation of lymphocyte responses in vitro. V. Suppressor activity of adherent and nonadherent rat lymphoid cells. Cell Immunol. 1973 Oct;9(1):12–24. doi: 10.1016/0008-8749(73)90163-9. [DOI] [PubMed] [Google Scholar]
  9. Folch H., Yoshinaga M., Waksman B. H. Regulation of lymphocyte responses in vitro. 3. Inhibition by adherent cells of the T-lymphocyte response to phytohemagglutinin. J Immunol. 1973 Mar;110(3):835–839. [PubMed] [Google Scholar]
  10. Gaut Z. N., Baruth H., Randall L. O., Ashley C., Paulsrud J. R. Stereoisomeric relationships among anti-inflammatory activity, inhibition of platelet aggregation, and inhibition of prostaglandin synthetase. Prostaglandins. 1975 Jul;10(1):59–66. doi: 10.1016/0090-6980(75)90093-3. [DOI] [PubMed] [Google Scholar]
  11. Gordon D., Bray M. A., Morley J. Control of lymphokine secretion by prostaglandins. Nature. 1976 Jul 29;262(5567):401–402. doi: 10.1038/262401a0. [DOI] [PubMed] [Google Scholar]
  12. Greaves M., Janossy G., Doenhoff M. Selective triggering of human T and B lymphocytes in vitro by polyclonal mitogens. J Exp Med. 1974 Jul 1;140(1):1–18. doi: 10.1084/jem.140.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hallberg T., Gurner B. W., Coombs R. R. Opsonic adherence of sensitized ox red cells to human lymphocytes as measured by rosette formation. Int Arch Allergy Appl Immunol. 1973;44(4):500–513. doi: 10.1159/000230956. [DOI] [PubMed] [Google Scholar]
  14. Henney C. S., Bourne H. R., Lichtenstein L. M. The role of cyclic 3',5' adenosine monophosphate in the specific cytolytic activity of lymphocytes. J Immunol. 1972 Jun;108(6):1526–1534. [PubMed] [Google Scholar]
  15. Hubert C., Delespesse G., Govaerts A. Concanavalin A-activated suppressor cells in normal human peripheral blood lymphocytes. Clin Exp Immunol. 1976 Oct;26(1):95–98. [PMC free article] [PubMed] [Google Scholar]
  16. Katz S. I., Parker D., Turk J. L. B-cell suppression of delayed hypersensitivity reactions. Nature. 1974 Oct 11;251(5475):550–551. doi: 10.1038/251550a0. [DOI] [PubMed] [Google Scholar]
  17. Keller R. Major changes in lymphocyte proliferation evoked by activated macrophages. Cell Immunol. 1975 Jun;17(2):542–551. doi: 10.1016/s0008-8749(75)80058-x. [DOI] [PubMed] [Google Scholar]
  18. Koopman W. J., Gillis M. H., David J. R. Prevention of MIF activity by agents known to increase cellular cyclic AMP. J Immunol. 1973 Jun;110(6):1609–1614. [PubMed] [Google Scholar]
  19. Lomnitzer R., Rabson A. R., Koornhof H. J. The effects of cyclic AMP on leucocyte inhibitory factor (LIF) production and on the inhibition of leucocyte migration. Clin Exp Immunol. 1976 Apr;24(1):42–48. [PMC free article] [PubMed] [Google Scholar]
  20. Melmon K. L., Bourne H. R., Weinstein Y., Shearer G. M., Kram J., Bauminger S. Hemolytic plaque formation by leukocytes in vitro. Control by vasoactive hormones. J Clin Invest. 1974 Jan;53(1):13–21. doi: 10.1172/JCI107530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Panush R. S. Effects of certain antirheumatic drugs on normal human peripheral blood lymphocytes. Inhibition of mitogen- and antigen-stimulated incorporation of tritiated thymidine. Arthritis Rheum. 1976 Sep-Oct;19(5):907–917. doi: 10.1002/art.1780190512. [DOI] [PubMed] [Google Scholar]
  22. Plescia O. J., Smith A. H., Grinwich K. Subversion of immune system by tumor cells and role of prostaglandins. Proc Natl Acad Sci U S A. 1975 May;72(5):1848–1851. doi: 10.1073/pnas.72.5.1848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Potter M. R., Moore M. The effect of adherent and phagocytic cells on human lymphocyte PHA responsiveness. Clin Exp Immunol. 1977 Jan;27(1):159–164. [PMC free article] [PubMed] [Google Scholar]
  24. Quagliata F., Lawrence V. J., Phillips-Quagliata J. M. Prostaglandin E 1 as a regulator of lymphocyte function. Selective action on B lymphocytes and synergy with procarbazine in depression of immune responses. Cell Immunol. 1973 Mar;6(3):457–465. doi: 10.1016/0008-8749(73)90044-0. [DOI] [PubMed] [Google Scholar]
  25. Raz A. Interaction of prostaglandins with blood plasma proteins. Comparative binding of prostaglandins A 2 , F 2 and E 2 to human plasma proteins. Biochem J. 1972 Nov;130(2):631–636. doi: 10.1042/bj1300631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Robinson D. R., Smith H., McGuire M. B., Levine L. Prostaglandin synthesis by rheumatoid synovium and its stimulation by colchicine. Prostaglandins. 1975 Jul;10(1):67–85. doi: 10.1016/0090-6980(75)90094-5. [DOI] [PubMed] [Google Scholar]
  27. Shou L., Schwartz S. A., Good R. A. Suppressor cell activity after concanavalin A treatment of lymphocytes from normal donors. J Exp Med. 1976 May 1;143(5):1100–1110. doi: 10.1084/jem.143.5.1100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Smith J. L., Forbes I. J. Use of human lymphocytes in studies of drug action. Nature. 1967 Jul 29;215(5100):538–539. doi: 10.1038/215538a0. [DOI] [PubMed] [Google Scholar]
  29. Smith J. W., Steiner A. L., Parker C. W. Human lymphocytic metabolism. Effects of cyclic and noncyclic nucleotides on stimulation by phytohemagglutinin. J Clin Invest. 1971 Feb;50(2):442–448. doi: 10.1172/JCI106511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Twomey J. J., Laughter A. H., Farrow S., Douglass C. C. Hodgkin's disease. An immunodepleting and immunosuppressive disorder. J Clin Invest. 1975 Aug;56(2):467–475. doi: 10.1172/JCI108113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Vane J. R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232–235. doi: 10.1038/newbio231232a0. [DOI] [PubMed] [Google Scholar]
  32. Waldmann T. A., Durm M., Broder S., Blackman M., Blaese R. M., Strober W. Role of suppressor T cells in pathogenesis of common variable hypogammaglobulinaemia. Lancet. 1974 Sep 14;2(7881):609–613. doi: 10.1016/s0140-6736(74)91940-0. [DOI] [PubMed] [Google Scholar]
  33. Webb D. R., Jr, Jamieson T. Control of mitogen-induced transformation: characterization of a splenic suppressor cell and its mode of action. Cell Immunol. 1976 Jun 1;24(1):45–57. doi: 10.1016/0008-8749(76)90130-1. [DOI] [PubMed] [Google Scholar]
  34. Webb D. R., Osheroff P. L. Antigen stimulation of prostaglandin synthesis and control of immune responses. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1300–1304. doi: 10.1073/pnas.73.4.1300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Yu D. T. Human lymphocyte subpopulation: early and late rosettes. J Immunol. 1975 Jul;115(1):91–93. [PubMed] [Google Scholar]
  36. Zimecki M., Webb D. R. The regulation of the immune response to T-independent antigens by prostaglandins and B cells. J Immunol. 1976 Dec;117(6):2158–2164. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES