Influence of PGE2 and LTB4 on CD8+ Thymocytes

  • Norbert Gualde
  • Richard Daculsi
  • Isabelle Hostein
  • Dominique Vaillier
  • Frédéric Buffière
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Arachidonic acid oxygenation products were considered as mediators mostly involved in inflammation, hypersensitivity and pain. Recently eicosanoids have been shown to participate in the immunoregulation. At the very beginning, investigators were interested by studying the role of arachidonic acid derivatives on differentiated lymphocytes obtained from the blood or variable peripheral lymphoid organs, more recently some studies focused on the effect of these metabolites on differentiation and maturation of immature lymphoid cells such as thymocytes. Since the thymus plays a central role for T cell physiology and function [1,2] the question remains to know if arachidonic acid metabolites which are producted within the thymus have a critical function in determining the differentiation and maturation of thymocytes. For instance it was reported that eicosanoids are produced by thymic macrophages [3,4], phagocytic cells of the thymic reticulum [5], thymic epithelial cells [6] and thymic nurse cells [7]. The production of eicosanoids by thymocytes themselves is more controversial [8, 9, 10]. Therefore we were interested in the study of eicosanoids production by the cells of the thymus microenvironment trying to determine what is the actual production of arachidonic acid derivatives whithin the thymus. For that purpose we produced thymus-macrophage hybridoma and assessed the synthesis of eicosanoids, and because the production of lipoxygenase metabolites is less clear we also studied the 5-lipoxygenase mRNA expression among thymic cells.


Thymic Epithelial Cell Arachidonic Acid Metabolite Thymidine Uptake Immature Thymocyte Thymus Microenvironment 
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  1. 1.
    Von Boehmer H, Kisielow P. Self-non self discrimination by T cells. Science 1990; 248: 1369–73.CrossRefGoogle Scholar
  2. 2.
    Sprent J. 1989. T lymphocytes and the thymus. In: Paul WE, ed. Fundamental Immunology, Second Edition. NY: Raven Press, 1989: 69–93.Google Scholar
  3. 3.
    Gallily R, Zeira M, Stain I. Thymus-derived macrophages in long-term culture: release of IL-1, stimulation of MLR and expresion of tumoricidal activity. Immunology 1985; 55: 165–72.PubMedGoogle Scholar
  4. 4.
    Delebassée SF, Cogny Van Weydevelt F, Gualde N. Effect of arachidonic acid metabolites on thymus tolerance. Ann NY Acad Sci 1988; 524: 227–39.CrossRefPubMedGoogle Scholar
  5. 5.
    Homo-Delarche F, Duval D, Papiernik M. Prostaglandin production by phagocytic cells of the mouse reticulum in culture and its modulation by indomethacin and corticosteroids. J Immunol 1985; 135: 506–12.PubMedGoogle Scholar
  6. 6.
    Munoz-Blay T, Nieburgs AC, Cohen S. Thymic epithelium in vitro. Cell Immunol. 1987; 109: 371–83.CrossRefPubMedGoogle Scholar
  7. 7.
    McCormack JE, Kappler J, Marrack P, Westcott JY. Production of prostaglandin E2 and prostacyclin by thymic nurse cells in culture. J Imunol 1991; 146: 239–43.Google Scholar
  8. 8.
    Rinaldi-Garaci C, Jezzi T, Baldassarre AM, Dardenne M, Bach JF, Garaci E. Effect of thymulin on intracellular cyclic nucleotides and prostaglandin E2 in peanut agglutinin-fractionnated thymocytes Eur J Immunol 1985; 15: 548–52.Google Scholar
  9. 9.
    Duval D, Effect of dexamethasone on arachidonate metabolism in isolated mouse thymocytes. Prostaglandins Leukotrienes Essential Fatty Acids 1989; 37: 149–56.CrossRefGoogle Scholar
  10. 10.
    Duval D, Huneau JF, Homo-Delarche F. Effect of serum on the metabolism of exogenous arachidonic acid by phagocytic cells of the mouse thymic reticulum. Prost. Leuk Med 1986; 23: 67–83.CrossRefGoogle Scholar
  11. 11.
    Papiernik M, Penit C, El Rouby S. Control of prothymocyte proliferation by thymic accesory cells. Eur J Immunol 1987; 17: 1303–10.CrossRefPubMedGoogle Scholar
  12. 12.
    Chomczynski P, Sacchi N. Single step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Ann Biochem 1987; 162: 156–9.CrossRefGoogle Scholar
  13. 13.
    Nossal GJV. Cellular mechanisms of immunologic tolerance Ann Rev Immunol 1983; 1: 33–62.CrossRefGoogle Scholar
  14. 14.
    Blackman M, Kappler J, Marrack P. The role of the T cell receptor in positive and negative selection of developing T cells. Science 1990; 248: 1335–41.CrossRefPubMedGoogle Scholar
  15. 15.
    Schwartz RH. A cell culture model for T lymphocyte clonal anergy. Science 1990; 248: 1349–56.CrossRefPubMedGoogle Scholar
  16. 16.
    Penit C, Vasseur F. Cell proliferation and differentiation in the fetal and early postnatal mouse thymus. J Immunol 1989; 141: 3369–77.Google Scholar
  17. 17.
    Scollay R, Bartlett P, Shortman K T-cell development in the adult murine thymus: changes in the expression of the surface antigens Ly2, L3T4 and B2A2 during development from early precursor cells to emigrant. Immunol Rev 1984; 80: 103–27.CrossRefGoogle Scholar
  18. 18.
    Crispe IN, Moore MW, Husman LA, Smith L, Bevan MJ, Shimonkevitz RP. Differentiation potential of subsets of CD4–8- thymocytes. Nature 1987; 329: 336–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Dennings SM, Kurtzberg J, Le PT, Tuck D, Singer KH, Haynes BF. Human thymic epithelial cells directly induce activation of autologous immature thymocytes. Proc Natl Acad Sci USA 1988; 85: 3125–9.CrossRefGoogle Scholar
  20. 20.
    Ceredig R, Glasebrook AL, Macdonald HR. Phenotypic and functional properties of murine thymocytes. I. Precursors of cytolytic T lymphocytes and interleukin 2-producing cells are all contained within a subpopulation of “mature” thymocytes as analyzed by monoclonal antibodies and flow microfluorometry. J Exp Med 1982; 155: 358–62.CrossRefPubMedGoogle Scholar
  21. 21.
    Hu-Li JE, Shevach EM, Mizuguchi J, Ohara J, Mosmann T, Paul WE. B-cell stimulatory factor 1 (interleukin4) is a potent costimulant for normal resting T lymphocytes. J Exp Med 1981; 165: 157–62.CrossRefGoogle Scholar
  22. 22.
    Cohen IR, Globerson A, Feldman M. Autosensitization in vitro. J Exp Med 1971; 133: 834–45.CrossRefPubMedGoogle Scholar
  23. 23.
    Cohen IR, Wekerle H. Regulation of autosensitization. The immune activation and specific inhibition of self-recognizing thymus-derived lymphocytes. J Exp Med 1973; 137: 224–38.CrossRefPubMedGoogle Scholar
  24. 24.
    Guilbert B, Dighiero D, Avrameas S. Naturally occurring antibodies against nine common antigens in human sera. I. Detection, isolation and characterization. J Immunol 1982; 128: 2779–92.PubMedGoogle Scholar
  25. 25.
    Dighiero G, Limbery P, Mazié JC, Rouyre S, Butler-Browne GS, Whalen RG, Avrameas S. Marine hybridomas secreting natural monoclonal antibodies reacting with self antigens. J Immunol 1983; 131: 2267–74.PubMedGoogle Scholar
  26. 26.
    Champion BR, Varey AM, Katz D, Cooke A, Roitt IM. Autoreactive T-cell lines specific for mouse thyroglobulin. Immunology 1985; 54: 513–9.PubMedGoogle Scholar
  27. 27.
    Karray S, Lymberi P, Avrameas S, Coutinho A. Quantitative evidence against inactivation of self-reactive B-cell clones. Scand J Immunol 1986; 23: 475–80.CrossRefPubMedGoogle Scholar
  28. 28.
    Hooper DC. Self-tolerance for erythrocytes is not maintained by clonal depletion of T helper cells. Immunol. Today 1987; 8: 327–30.CrossRefGoogle Scholar
  29. 29.
    Hooper DC, Taylor RB. Specific helper T cell reactivity against autologous erythrocytes implies that self tolerance need not depend on clonal deletion. Eur J Immunol 1987; 17: 797–802.CrossRefPubMedGoogle Scholar
  30. 30.
    Gualde N, Cogny Van Weydevelt F, Buffière F, Jauberteau MO, Daculsi R, Vaillier D. Influence of LTB4 on CD4-CD8- thymocytes. Evidence that LTB4 plus IL-2 generate CD8+ suppressor thymocytes involved in tolerance to self (in press).Google Scholar
  31. 31.
    Yverson M, Ptak W, Green D, Gershon R. Role of contrasuppression in the adoptive transfer of immunity. J Exp Med 1983; 158: 982–7.CrossRefGoogle Scholar
  32. 32.
    Bergstrom S, Samuelsson B. Isolation of prostaglandin El from calf thymus. Prostaglandins and related factors 20. Acta Chem Scand 1963; 17: 282–7.CrossRefGoogle Scholar
  33. 33.
    Tomar RH, Darrow T, John PA. Response to and production of prostaglandin by murine thymus, spleen, bone marrow, and lymph node cells. Cell Immunol. 1981; 60: 335–46.CrossRefPubMedGoogle Scholar
  34. 34.
    Bonney RJ, Humes JL. Physiological and pharmacological regulation of prostaglandin and leukotriene production by macrophages. J Leukocyt Biol 1984; 35: 1–10.Google Scholar
  35. 35.
    Delebassée S, Gualde N. Effect of arachidonic acid metabolites on thymocyte proliferation. Ann Inst Pasteur/Immunology 1988; 139: 383–99.CrossRefGoogle Scholar
  36. 36.
    Delebassée S, Cogny Van Weydevelt F, Gualde N. Effects of eicosanoïds on thymocyte physiology. Immunobiol 1987; 3: 227–8.Google Scholar
  37. 37.
    Wisocki LJ, Sato VL.“Panning” for lymphocytes a method for cell selection. Proc Natl Acad Sci USA. 1978; 75: 2844–8.CrossRefGoogle Scholar
  38. 38.
    Hodgkin PD, Cupp J, Zlotnik A, Howard M. IL-2, IL-6, and IFN-y have distinct effects on the IL-4 plus PMA-induced proliferation of thymocytes subpopulations. Cell Immunol 1990; 126: 57–68.CrossRefPubMedGoogle Scholar
  39. 39.
    Bockman RS. PGE inhibition of T lymphocyte colony formation. J Clin Invest 1979; 64: 812–21.CrossRefPubMedGoogle Scholar
  40. 40.
    Gualde N, Cook J-M, Guibert F. Effect of PGE2 and LTB4 on vicia villosa binding lymphocytes. APMIS 1988; 96: 531–6.CrossRefPubMedGoogle Scholar
  41. 41.
    Nieburgs AC, Korn JH, Picciano PT, Cohen S. PGE2 production by the thymus. Cell Immunol 1987; 108: 396–401.CrossRefPubMedGoogle Scholar
  42. 42.
    Sun L, Piltch AS, Liu P-S, Johnson LA, Hayashi J. Thymocytes stimulate metabolism of arachidonic acid in rat thymic epithelial cells. Cell Immunol 1990; 131: 86–97.CrossRefPubMedGoogle Scholar
  43. 43.
    Goodwin JS, Ceuppens J. Regulation of the immune response by prostaglandins. J Clin Immunol 1983; 3: 295–315.CrossRefPubMedGoogle Scholar
  44. 44.
    Gualde N, Goodwin JS. Effects of prostaglandin E2 and preincubation on lectinstimulated proliferation of human T cell subsets. Cell Immunol 1982; 70: 378–8.Google Scholar
  45. 45.
    Novagrodsky A, Rubin AL, Stenzel KH. Selective suppression by adherent cells, prostaglandins, and cyclicAMP analogues of blastogenesis induced by different mitogens. J Immunol 1979; 122: 1–8.Google Scholar
  46. 46.
    Chouaib S, Fradelizi D. The mechanism of inhibition of human IL-2 production. J Immunol. 1882; 129: 2463–8.Google Scholar
  47. 47.
    Rappaport RS, Dodge GR. Prostaglandin E inhibits the production of human interleukin 2. J Exp Med 1982; 155: 943–8.Google Scholar
  48. 48.
    De La Hera A, Toribio ML, Marquez C, Martinez AC. Interleukin 2 promotes growth and cytolytic activity in human T3+4–8- thymocytes. Proc Nat Acad Sci USA 1985; 82: 6268–71.CrossRefPubMedGoogle Scholar
  49. 49.
    Howard M, Farrar JJ, Hilfiker M, Johnson B, Tokatsu K, Hamaoka T, Paul WE. Identification of a T cell-derived B cell growth factor distint from interleukin 2. J Exp Med 1982; 155: 914–27.CrossRefPubMedGoogle Scholar
  50. 50.
    Zlatnik A, Ransom J, Frank G, Fischer M, Howard M. Interleukin 4 is a gowth factor for activated thymocytes: possible role in T-cell ontogeny. Proc Nat Acad Sci USA 1987; 84: 3856–60.CrossRefGoogle Scholar
  51. 51.
    Rothenberg EV. Death and transfiguration of cortical thymocytes, a reconsideration. Immunol Today 1990; 11: 116–9.CrossRefPubMedGoogle Scholar
  52. 52.
    Lo D, Ron Y, Sprent J. Induction of MHC-restricted specificity and tolerance in the thymus. Immunol Res 1986; 5: 221–32.CrossRefPubMedGoogle Scholar
  53. 53.
    Sprent J, Lo D, Gao EK, Ron Y. T cell selection in the thymus. Immunol Rev 1988; 101: 173–90.CrossRefPubMedGoogle Scholar
  54. 54.
    Nossal GJV. Cellular mechanisms of immunological tolerance. In: Paul EW, Fathman CG and Metzger H, eds. Ann Rev Immunol Annual Reviews Inc. Palo Alto. CA. 1983: 33–62.Google Scholar
  55. 55.
    Gibson J, Basten A, Walker KZ, Loblay RH. A role for suppressor T cells in induction of self-tolerance. Proc Nati Acad Sci USA 1985; 82: 5150–4.CrossRefGoogle Scholar
  56. 56.
    Miller RD, and C.E. Calkins CE. Suppressor T cells and self-tolerance active suppression required for normal regulation of anti-erythrocyte autoantibody responses in spleen cells from non autoimmune mice. J Immunol 1988; 140: 3779–85.PubMedGoogle Scholar
  57. 57.
    Rola-Pleszczynski M. Differential effects of leukotriene B4 ont T4+ and T8+ lymphocyte phenotype and immunoregulatory functions. J Immunol 1985; 135: 1357–60.PubMedGoogle Scholar
  58. 58.
    Atluru D, Goodwin JS. Control of polyclonal immunoglobulin production from human lymphocytes by leukotrienes; leukotriene B4 induces an OKT8+ radiosensitive suppressor cell from resting human OKT8- T cells. J Clin Invest 1984; 74: 1444–50.CrossRefPubMedGoogle Scholar
  59. 59.
    Gualde N, Atluru D, Goodwin JS. Effect of lipoxygenase metabolites of arachidonic acid on proliferation of human T cells and T cell subsets. J Immunol 1985; 134: 1125–9.PubMedGoogle Scholar
  60. 60.
    Rola-Pleszczynski M, Borgeat P, Sirois P. Leukotriene B4 induces human suppressor lymphocytes. Biochim Biophys Res Commun 1982; 4: 1531–7.CrossRefGoogle Scholar
  61. 61.
    Lejeune-Ledant G. Transplantation antigens, production of haemagglutinins and inhibition of the haemagglutination reaction. In: Wolstenholme GEW, Cameron MP, eds. Ciba Foundation Symposium on Transplantation. London: Churchill JA, 1962: 25–44.CrossRefGoogle Scholar
  62. 62.
    Mexmain S, Cook JM, Aldigier JC, Gualde N, Rigaud M. Thymocyte cyclicAMP response to treatment with metabolites issued from the lipoxygenase pathway. J Immunol 1895; 135: 1361–5.Google Scholar
  63. 63.
    Papiernik M, Homo-Delarche F. Thymic reticulum in culture secrete both prostaglandin E2 and interleukin 1 which regulate thymocyte proliferation. Eur J Immunol 1983; 13: 689–92.CrossRefPubMedGoogle Scholar
  64. 64.
    McConkey DJ, Orrenius S, Jondal M. Agents that elevate cAMP stimulate DNA fragmentation in thymocytes. J Immunol 1990; 145: 1227–30.PubMedGoogle Scholar
  65. 65.
    Suzuki K, Tadakuma T, Kizaki H. Modulation of thymocyte apoptosis by isoproterenol and prostaglandin E2. Cell Immunol 1991; 134: 235–40.CrossRefPubMedGoogle Scholar
  66. 66.
    Papiemik M, Nabarra B, Savino W, Pontoux C, Barbey S. Thymic reticulum in mice. II. Culture and characterization of non epithelial phagocytic cells of the thymic reticulum: their role in the syngeneic stimulation of thymic medullary lymphocytes. Eur J Immunol 1983; 13: 147–58.CrossRefGoogle Scholar
  67. 67.
    Gualde N, Rigaud M, Bach JF. Stimulation of prostaglandin synthesis by the thymic factor (FTS). Cell Immunol 1982; 70: 362–7.CrossRefPubMedGoogle Scholar
  68. 68.
    Rinaldi-Garaci C, Del Globo V, Favalli C, Garaci E, Bistoni F, Jaffe B. Induction of serum thymic-like activity in adult thymectomized mice by a synthetic analog of PGE2. Cell Immunol 1982; 72: 97–101.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Norbert Gualde
    • 1
    • 2
  • Richard Daculsi
    • 1
  • Isabelle Hostein
    • 1
  • Dominique Vaillier
    • 1
  • Frédéric Buffière
    • 1
    • 3
  1. 1.URA CNRS 1456Université de Bordeaux 2BordeauxFrance
  2. 2.Fondation BergoniéBordeauxFrance
  3. 3.Centre Régional de Transfusion SanguineBordeauxFrance

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