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Inhibitory effects of cyclosporin A on lymphocyte activation

  • Chapter
Cyclosporin

Abstract

Cyclosporin A (CsA) was first identified in the early 1970s by Dr J. F. Borel and colleagues of Sandoz Ltd as a compound in the culture broths of the fungi Tolypodadium inflatum and Cylindrocarpon lucidum that showed strong in vivo immunosuppressive activity in micer but was otherwise well tolerated. Their influential publication on the properties of CsA in 19761 led to successful clinical trials, and the drug is now in routine use in organ transplantation. It also shows promise in the prevention or treatment of some conditions with an autoimmune basis (discussed in subsequent chapters of this volume). It was very quickly apparent that CsA differed in its mechanism of action from pre-existing immunosuppressive drugs, in that at therapeutic concentrations it showed no general inhibition of cell proliferation and was not cytotoxic to lymphocytes.

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References

  1. Borel, J. F., Feurerr C., Gubler, H. U. and Stahelin, H. (1976) Biological effects of cyclosporin A: a new antifymphocytic agent. Agents Actions, 6, 468–475

    Article  PubMed  CAS  Google Scholar 

  2. Von Wartburg, A. and Traber, R. (1986) Chemistry of the natural cyclosporin metabolites. Progr. Allergy, 38, 28–45

    Google Scholar 

  3. Wenger, R. M. (1986) Synthesis of Ciclosporin and analogues: structural and conformational requirements for immunosuppressive activity. Progr. Allergy, 38, 46–64

    CAS  Google Scholar 

  4. Hiestand, P. C., Gunn, H. C., Gales, J. M., Ryffel B. and Borel, J. F. (1985) Comparison of the pharmacological profiles of cyclosporine, (Nva2)-cyclosporine and (Val2)-dihydrocy-closporine. Immunology, 55, 249–255

    PubMed  CAS  Google Scholar 

  5. Borel J. F. (1986) Ciclosporin and its future. Progr. Allergy, 38, 9–18

    CAS  Google Scholar 

  6. Wiesinger, D. and Borel, J. F. (1979) Studies on the mechanism of action of cyclosporin A. Immunobiology, 156, 454–463

    Google Scholar 

  7. Kay, J. E. and Benzie, C. R. (1983) Effects of cyclosporin A on the metabolism of unstimulated and mitogen-activated lymphocytes. Immunology, 49, 153–160

    PubMed  CAS  Google Scholar 

  8. Kay, J. E. and Benzie, C. R. (1986) Lymphocyte activation by OKT3: cyclosporine sensitivity and synergism with phorbol ester. Immunology, 57, 195–199

    PubMed  CAS  Google Scholar 

  9. Dongworth, D. W. and Klaus, G. G. B. (1982) Effects of cyclosporin on the immune system of the mouse. I. Evidence for a direct selective effect of cyclosporin A on B cells responding to anti-immunoglobulin antibodies. Eur. J. Immunol., 12, 1018–1022

    Article  PubMed  CAS  Google Scholar 

  10. Paavonen, T. and Hayry, P. (1980) Effect of cyclosporin A on T-dependent and T-independent immunoglobulin synthesis in vitro. Nature (Lond.), 287, 542–544

    Article  CAS  Google Scholar 

  11. Van Buren, C. T., Kerman, R., Agostino, D., Payne, W., Flechner, S. and Kahan, B. D. (1982) The cellular target of cyclosporin A actions in humans. Surgery, 80, 167–173

    Google Scholar 

  12. Lafferty, K. J., Gill, R. and Babcock, S. (1986) Tolerance induction in adult animals. Progr. Allergy, 38, 247–257

    CAS  Google Scholar 

  13. Hess, A. D. and Colombani, P. M. (1986) Mechanism of action: in vitro studies. Progr. Allergy, 38, 198–221

    CAS  Google Scholar 

  14. Orosz, C C., Roopenian, D. C., Widmer, M. B. and Bach, F. H. (1983) Analysis of cloned T cell function. II. Differentia] blockade of various cloned T cell functions by cyclosporine. Transplantation, 36, 706–711

    Article  PubMed  CAS  Google Scholar 

  15. Damjanovich, S., Aszalos, A., Mulheim, S., Balazs, M. and Matyus, L. (1986) Cytoplasmic membrane potential of mouse lymphocytes is decreased by cyclosporins. Mol Immunol., 23, 175–180

    Article  PubMed  CAS  Google Scholar 

  16. Gelfand, E. W., Cheung, R. K. and Mills, C. B. (1987) The cyclosporins inhibit lymphocyte activation at more than one site. J. Immunol., 138, 1115–1120

    PubMed  CAS  Google Scholar 

  17. Manca, F., Kurtkl, A. and Celada, F. (1985) Inhibition of the accessory function of murine macrophages in vitro by cyclosporine. Transplantation, 39, 644–649

    Article  PubMed  CAS  Google Scholar 

  18. Varey, A-M., Champion, B. R. and Cooke, A. (1986) Cyclosporine affects the function of antigen-presenting cells. Immunoloy, 57, 111–114

    CAS  Google Scholar 

  19. Knight, S. C., Balfour, B., O’Brien, J. and Buttifant, L. (1986) Sensitivity of veiled (dendritic) cells to cyclosporine. Transplantation, 41, 96–100

    Article  PubMed  CAS  Google Scholar 

  20. Knight, S. C. and Bedford, P. A. (1987) Effects of cyclosporine and retinoic acid on dendritic cell function. Transplant. Proc., 19, 320–323

    PubMed  CAS  Google Scholar 

  21. Knight, S. C., Roberts, M., Macatonia, S. E. and Edwards, A. J. (1988) Blocking of acquisition and presentation of antigen by dendritic cells with cyclosporine. Transplantation (Suppl), 46, 48S–53S

    PubMed  Google Scholar 

  22. Kay, J. E. and Benzie, C. R. (1984) Rapid loss of sensitivity of mitogen-induced lymphocyte activation to inhibition by cyclosporin A. Cell. Immunol., 87, 217–224

    Article  PubMed  CAS  Google Scholar 

  23. Bunjes, D., Hardt, C., Rollinghoff, M. and Wagner, H. (1981) Cyclosporin A mediates immunosuppression of primary cytotoxic T cell responses by impairing the release of interleukin-1 and interleukin-2. Eur. J. Immunol., 11, 657–661

    Article  PubMed  CAS  Google Scholar 

  24. Wang, B. S., Heacock, E. H., Collins, K. H., Hutchinson, I. F., Tilney, N. L. and Mannick, J. A. (1981) Suppressive effects of cyclosporin A on the induction of alloreactivity in vitro and in vivo. J. Immunol., 127, 89–93

    PubMed  CAS  Google Scholar 

  25. O’Garra, A., Warren, D. J., Holman, M., Popham, A. M., Sanderson, C. J. and Klaus, G. G. B. (1986) Effects of cyclosporine on responses of murine B cells to T cell-derived lymphokines. J. Immunol., 137, 2220–2224

    PubMed  Google Scholar 

  26. Isakov, N., Maey, M. I., Scholz, W. and Altman, A. (1987) T lymphocyte activation: the role of protein kinase C and the bifurcating inositol phospholipid signal transduction pathway. Immunol Rev., 95, 89–111

    Article  PubMed  CAS  Google Scholar 

  27. King, S. (1988) An assessment of phosphoinositide hydrolysis in antigenic signal transduction in lymphocytes. Immunology, 65, 1–7

    PubMed  CAS  Google Scholar 

  28. Zilberman, Y., Howe, L. R., Moore, J. P., Hesketh, T. R. and Metcalfe, J. G (1987) Calcium regulates inositol 1,3,4,5-tetrakisphophate production in lysed thymocytes and in intact cells stimulated with concanavalin A. EMBO J., 6, 957–962

    CAS  Google Scholar 

  29. Truneh, A., Albert, F., Golstein, P. and Schmitt-Verhulst, A-M. (1985) Early steps of lymphocyte activation bypassed by synergy between calcium ionophores and phorbol ester. Nature (Lond.), 313, 318–320

    Article  CAS  Google Scholar 

  30. Kaibuchi, K., Takai, T. and Nishizuka, Y. (1985) Protein kinase C and calcium ion in mitogenic response of macrophage-depleted human peripheral lymphocytes. J. Biol Chem., 260, 1366–1369

    PubMed  CAS  Google Scholar 

  31. Rosoff, P. M., Savage, N. and Dinarello, C. A. (1988) Interleukin-1 stimulates diacylglycerol production in T lymphocytes by a novel mechanism. Cell, 54, 73–81

    Article  PubMed  Google Scholar 

  32. Bijsfcerbosch, M. K. and Klaus, G. G. B. (1985) Cyclosporine does not inhibit mitogen-induced inositol phospholipid degradation in mouse lymphocytes. Immunology, 56, 435–440

    Google Scholar 

  33. Mizushima, Y., Kosaka, H., Sakuma, S., Kanda, K., Itoh, K., Osugi, T., Mizushima, A., Hamaoka, T., Yoshida, H., Sobue, K. and Fujiwara, H. (1987) Cyclosporin A inhibits late steps of T lymphocyte activation after transmembrane signalling. J. Biochem., 102, 1193–1201

    PubMed  CAS  Google Scholar 

  34. Palacios, R. (1982) Concanavalin A triggers T lymphocytes by directly interacting with their receptors for activation. J. Immunol., 128, 337–342

    PubMed  CAS  Google Scholar 

  35. Kay, J. E., Meehan, R. T. and Benzie, C. R. (1983) Activation of T lymphocytes by 12-O-tetradecanoylphorbol-13-acetate is resistant to inhibition by cyclosporin A. Immunol Lett., 7, 151–156

    Article  PubMed  CAS  Google Scholar 

  36. Kay, J. E., Benzie, C. R. and Borghetti, A. F. (1983) Effect of cyclosporin A on lymphocyte activation by the calcium ionophore A23187. Immunology, 50, 441–46

    PubMed  CAS  Google Scholar 

  37. Szamel, M., Martin, A. and Resch, K. (1985) Inhibition of lymphocyte activation by cyclosporin A: interference with the early activation of the membrane phospholipid metabolism in rabbit lymphocytes stimulated with concanavalin A, anti-rabbit immunoglobulin or the Ca2+ ionophore A23187. Cell. Immunol., 93, 239–249

    Article  PubMed  CAS  Google Scholar 

  38. Klaus, G. G. B. (1987) Cyclosporin as a probe for different modes of lymphocyte activation. Ann. Inst. Pasteur/Immunol., 138, 626–628

    Article  CAS  Google Scholar 

  39. Metcalfe, S. M. (1984) Cyclosporine does not prevent cytoplasmic calcium changes associated with lymphocyte activation. Transplantation, 38, 161–164

    Article  PubMed  CAS  Google Scholar 

  40. Wiskodi R., Weiss, A., Imboden, J., Kamin-Lewis, R. and Stobo, J. (1985) Activation of a human T cell line: a two stimulus requirement in the pre-translational events involved in the coordinate expression of interteukin-2 and gamma interferon genes. J. Immunol., 134, 1599–1603

    Google Scholar 

  41. Rosoff, P. M and Terres, G. (1986) Cyclosporin A inhibits Ca2+ dependent stimulation of the Na+/H+ antiport in human T cells. J. Cell Biol., 103, 457–463

    Article  PubMed  CAS  Google Scholar 

  42. Manger, B., Hardy, K. J., Weiss, A. and Stobo, J. D. (1986) Differential effect of cyclosporin A on activation signalling in human T cell lines. J. Clin. Invest., 77, 1501–1506

    Article  PubMed  CAS  Google Scholar 

  43. Kay, J. E., Benzie, C. R. and Gudgeon, M. C. Unpublished data.

    Google Scholar 

  44. Granelli-Piperno, A., Artdrus, L. and Steinman, R. M. (1986) Lymphokine and non-lymphokine mRNA levels in stimulated human T cells. J. Exp. Med., 163, 922–937

    Article  PubMed  CAS  Google Scholar 

  45. Goodier, M. R. and Kay, J. E. Unpublished data.

    Google Scholar 

  46. Miyawaki, T., Yachie, A., Ohzeki, S., Nagaoki, T. and Taniguchi, N. (1983) Cyclosporin A does not prevent expression of Tac antigen, a probable TCGF receptor molecule, on rnitogen-stimulated human T cells. J. Immunol., 130, 2737–2742

    PubMed  CAS  Google Scholar 

  47. Kronke, M., Leonard, W. J., Depper, J. M., Arya, S. K., Wong-Staal, F., Gallo, R. C., Waldmann, T. A. and Greene, W. C. (1984) Cyclosporin A inhibits T-cell growth factor gene expression at the level of mRNA transcription. Proc. Natl Acad. Sci. USA, 81, 5214–5218

    Article  PubMed  CAS  Google Scholar 

  48. Larsson, E-L. (1980) Cyclosporin A and dexamethasone suppress T cell responses by selectively acting at distinct sites of the triggering process. J. Immunol., 124, 2828–2833

    PubMed  CAS  Google Scholar 

  49. Lillehoj, H. S., Malek, T. R. and Shevach, E. M. (1984) Differential effect of cyclosporin A on the expression of T and B lymphocyte activation antigens. J. Immunol, 133, 244–250

    PubMed  CAS  Google Scholar 

  50. Reed, J. C., Abidi, A. H., Alpers, J. D., Hoover, R. G., Robb, R. J. and Nowell, P. C. (1986) Effect of cyclosporin A and dexamethasone on interleukin 2 receptor gene expression. J. Immunol., 137, 150–154

    PubMed  CAS  Google Scholar 

  51. Aiello, F. B., Maggiano, N., Larocca, L. M., Piantelli, M. and Musiani, P. (1986) Inhibitory effect of cyclosporin A on the OKT3-induced peripheral blood lymphocyte proliferation. Cell. Immunol., 97, 131–139

    Article  PubMed  CAS  Google Scholar 

  52. Szamel, M., Berger, P. and Resch, K. (1986) Inhibition of T lymphocyte activation by cyclosporin A: interference with the early activation of plasma membrane phospholipid metabolism. J. Immunol., 136, 264–269

    PubMed  CAS  Google Scholar 

  53. Fidelius, R. K., Laughter, A. R, Tworney, J. J., Taffet, S. M. and Haddox, M. K. (1984) The effect of cyclosporine on ornithine decarboxylase induction with mitogens, antigens and lymphokines. Transplantation, 37, 383–389

    Article  Google Scholar 

  54. Bunjes, D., Hardt, C., Rollinghoff, M. and Wagner, H. (1981) Cyclosporin A mediates immunosuppression of primary cytotoxic T cell responses by impairing the release of interleukin 1 and interleukin 2. Eur. J. Immunol., 11, 657–661

    Article  PubMed  CAS  Google Scholar 

  55. Kaufmann, Y., Chang, A. E., Robb, R. J. and Rosenberg, S. A. (1984) Mechanism of action of cyclosporin A: inhibition of lymphokine secretion studied with antigen-stimulated T cell hybridomas. J. Immunol., 133, 3107–3111

    PubMed  CAS  Google Scholar 

  56. Granelli-Piperno, A., Inaba, K. and Steinman, R. (1984) Stimulation of lymphokine release from T lymphoblasts. Requirement for mRNA synthesis and inhibition by cyclosporin A. J. Exp. Med., 160, 1792–1802

    Article  PubMed  CAS  Google Scholar 

  57. Elliott, J. F., Lin, Y., Mizel, S. B., Bleackley, R. C., Harnish, D. G. and Paetkau, V. (1984) Induction of interleukin 2 mRNA inhibited by cyclosporin A. Science, 226, 1439–1442

    Article  PubMed  CAS  Google Scholar 

  58. Herold, K. C., Lancki, D. W., Moldwin, R. L. and Fitch, F. W. (1986) Immunosuppressive effects of cyclosporin A on cloned T cells. J. Immunol., 136, 1315–1321

    PubMed  CAS  Google Scholar 

  59. Kalman, V. K. and Klimpel, G. R. (1983) Cyclosporin A inhibits the production of gamma interferon but does not inhibit production of virus-induced interferon alpha and beta. Cell. Immunol., 78, 122–129

    Article  PubMed  CAS  Google Scholar 

  60. Palados, R., Martinez-Maza, O. and De Ley, M. (1983) Production of human immune interferon studied at the single cell level. Origin, evidence of spontaneous secretion and effect of cydosporin A. Eur. J. Immunol., 13, 221–225

    Article  Google Scholar 

  61. Reem, G. H., Cook, L. A. and Vilcek, J. (1983) Gamma interferon synthesis by human thymocytes and T lymphocytes inhibited by cyclosporin A. Science, 221, 63–65

    Article  PubMed  CAS  Google Scholar 

  62. Bickel, M., Tsuda, H., Amstad, P., Evequoz, V., Mergenhagen, S. E., Wahl, S.M. and Piuznik, D. H. (1987) Differential regulation of colony simulating factors and interleukin 2 production by cyclosporin A, Proc. Natl. Acad. Sci. USA, 84, 3274–3277

    Article  PubMed  CAS  Google Scholar 

  63. Granelii-Piperho, A. (1988) Effects of cyclosporin A on T lymphocytes and accessory cells from human blood. Ahshr. 9th European Immunology Congress (Rome), p. 230

    Google Scholar 

  64. Shaw, J., Meerovitch, K., Elliott, J. F., Bleackley, R. C. and Paetkau, V. (1987) Induction, suppression and superinduction of lymphokine mRNA in T lymphocytes. Mol. Immunol., 24, 409–419

    Article  PubMed  CAS  Google Scholar 

  65. Brack, C., Mattaj, I. W., Gautschi, J. and Cammisuli, S. (1984) Cyclosporin A is a differential inhibitor of eukaryotic RNA polymerases. Exp. Cell Res., 151, 314–321

    Article  PubMed  CAS  Google Scholar 

  66. Andrus, L. and Lafferty, K. J. (1982) Inhibition of T cell activity by cyclosporin A. Scand. J. Immunol., 15, 449–458

    Article  CAS  Google Scholar 

  67. Thomson, A. W., Moon, D. K., Geczy, G L. and Nelson, D. S. (1983) Cyclosporin A inhibits lymphokine production, but not responses of macrophages to lymphokines. Immunology, 48, 291–299

    PubMed  CAS  Google Scholar 

  68. Helin, H. J. and Edgington, T. S. (1984) Cyclosporin A regulates monocyte/macrophage effector functions by affecting instructor T cells. Inhibition of monocyte procoagulant response to allogeneic stimulation. J. Immunol., 132, 1074–1076

    PubMed  CAS  Google Scholar 

  69. Havele, C. and Paetkau, V. (1988) Cyclosporme blocks the activation of antigen-dependent cytotoxic T lymphocytes directly by an IL-2-independent mechanism. J. Immunol., 140, 3303–3308

    PubMed  CAS  Google Scholar 

  70. Bendtzen, K. and Dinarello, C. A. (1984) Mechanism of action of cyclosporin A. Effect on T-cell-binding of interleukin 1 and antagonizing effect of insulin. Scand. J. Immunol., 20,43–51

    Article  PubMed  CAS  Google Scholar 

  71. Galatowicz, G., Benzie, C. R., Kay, J. E. and Soos, M. (1986) The role of insulin in lymphocyte activation. Biochem. Soc. Trans., 14, 326

    CAS  Google Scholar 

  72. LeGrue, S. J., Friedman, A. W. and Kahan, B. D. (1983) Binding of cyclosporine by human lymphocytes and phospholipid vesicles. J. Immunol., 131, 712–718

    PubMed  CAS  Google Scholar 

  73. Koponen, M. and Loor, F. (1983) Cytoplasmic lipid droplets as the possible eventual cellular fate of active forms of cyclosporin. Exp. Cell Res., 149, 499–512

    Article  CAS  Google Scholar 

  74. Merker, M. M. and Handschumacher, R. E. (1984) Uptake and nature of the intracellular binding of cyclosporin A in a murine thymoma cell line, BW5147. J. Immunol., 132, 3064–3070

    PubMed  CAS  Google Scholar 

  75. Handschumacher, R. E., Harding, M W., Rice, J., Drugge, R. J. and Speicher, D. W. (1984) Cyclophilin: a specific cytosolic binding protein for cyclosporin A. Science, 226, 544–547

    Article  PubMed  CAS  Google Scholar 

  76. Koletsky, A. J., Harding, M. W. and Handschumacher, R. E. (1986) Cyclophilin: distribution and variant properties in normal and neoplastic tissues, J. Immunol., 137, 1054–1059

    PubMed  CAS  Google Scholar 

  77. Haendler, B., Hofer-Warbinek, R. and Hofer, E. (1987) Complementary DNA for human T-cell cyclophilin. EMBO J., 6, 947–950

    PubMed  CAS  Google Scholar 

  78. Harding, M. W., Handschumacher, R. E. and Speicher, D. W. (1986) Isolation and amino acid sequence of cyclophilin. J. Biol. Chem., 261, 8547–8555

    PubMed  CAS  Google Scholar 

  79. Danielson, P. E, Forss-Petter, S., Brow, M. A, Calavetfca, L., Douglass, J., Milner, R. J. and Sutcliffe, J. G. (1988) plBl5: a cDNA clone of the rat mRNA encoding cyclophilin. DNA, 7, 261–267

    Article  PubMed  Google Scholar 

  80. Gschwendt, M., Kittstein, W. and Marks, F. (1988) Sequence homology between cyclophilin and elongation factor 2. Biochem. J., 256, 1061

    PubMed  CAS  Google Scholar 

  81. Colombani, P. M., Robb, A. and Hess, A. D. (1985) Cyclosporin binding to calmodulin: a possible site of action on T lymphocytes. Science, 228, 337–339

    Article  PubMed  CAS  Google Scholar 

  82. Hait, W. N., Harding, M. W. and Handschumacher, R. E. (1986) Calmodulin, cyclophilin and cyclosporin A. Science, 233, 987–988

    Article  PubMed  CAS  Google Scholar 

  83. LeGrue, S. J., Turner, R., Weisbrodt, N. and Dedman, J. R. (1986) Does the binding of cyclosporine to calmodulin result in immunosuppression? Science, 234, 68–71

    Article  PubMed  CAS  Google Scholar 

  84. Gudgeon, M. C., Benzie, C. R. and Kay, J. E. (1986) Role of Ca2+ and calmodulin in the inhibition of lymphocyte activation by cyclosporine. Biochem. Soc. Trans., 14, 1050–1051

    CAS  Google Scholar 

  85. Gudgeon, M. C. (1986) Studies on the mechanism of action of cyclosporin A. D.Phil, thesis, University of Sussex, pp. 136–149

    Google Scholar 

  86. Hess, A. D. and Colombani, P. N. (1987) Cyclosporin-resistant and -sensitive T lymphocyte subsets. Ann. Inst. Pasteur/Immunol, 138, 606–611 & 648–650

    Article  CAS  Google Scholar 

  87. Larson, D. F. (1986) Mechanism of action: antagonism of the prolactin receptor. Progr. Allergy, 38, 222–238

    CAS  Google Scholar 

  88. Hiestand, P. G, Melder, P., Nordmann, R., Glieder, A. and Permmongkol, C. (1986) Prolactin as a modulator of lymphocyte responsiveness provides a possible mechanism of action for cyclosporine. Proc.. Natl Acad. Sci. USA, 83, 2599–2603

    Article  PubMed  CAS  Google Scholar 

  89. Daniel, T. O and Ives, H. E. (1987) Cyclosporin A inhibits kinase C-independent activation of the Na+/H+ exchange by platelet-derived growlh factor and vanadate. Biochem. Biophys. Res. Commun., 145, 111–117

    Article  PubMed  CAS  Google Scholar 

  90. Slater, L. M., Sweet, P., Stupecky, M. and Gupta, S. (1986) Cyclosporin A reverses vincristine and daunorubicin resistance in acute lymphatic leukaemia in vifro. J. Clin. Invest., 77, 1405–1408

    Article  PubMed  CAS  Google Scholar 

  91. Nicchitta, G V., Kamoun, M. and Williamson, J. R. (1985) Cyclosporine augments receptor-mediated cellular Ca2+ fluxes in Isolated hepatocytes. J. Biol. Ckem., 260, 13613–13618

    CAS  Google Scholar 

  92. Pfeilschifter, J. and Ruegg, U. T. (1987) Cyclosporin A augments angiotensin II-stimulated rise in intracellular free calcium in vascular smooth muscle cells. Biochem. J., 248, 883–887

    PubMed  CAS  Google Scholar 

  93. Fournier, N., Ducet, G. and Crevat, A. (1987) Action of cyclosporine on mitochondrial calcium fluxes. J. Bioenerg. Biomembr., 19, 297–303

    Article  PubMed  CAS  Google Scholar 

  94. Crornpton, M., Ellinger, K and Costi, A. (1988) Inhibition by cyclosporin A of a Ca2+-dependent pore in heart mitochondria activated by inorganic phosphate and oxidative stress. Biochem. J., 255, 357–360

    Google Scholar 

  95. Gschwendt, M., Kittstein, W. and Marks, F. (1988) Effect of tumor promoting phorbol ester TPA on epidermal protein synthesis: stimulation of an elongation factor 2 phosphatase activity by TPA in vivo. Biochem. Biophys. Res. Commun., 153, 1129–1135

    Article  CAS  Google Scholar 

  96. Chisholm, P. M., Drayson, M. T., Cox, J. H. and Ford, W. L. (1985) The effects of cyclosporin on lymphocyte activation in a systemic graft-vs.-host reaction. Eur. J. Immunol., 15, 1054–1059

    Article  PubMed  CAS  Google Scholar 

  97. Klaus, G. G. B. and Chisholm, P. M. (1986) Does cyclosporine act in vivo as it does in vitro? Immunol. Today, 7, 101–103

    Article  CAS  Google Scholar 

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  1. John E. Kay
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  1. Immunopathology Laboratory, Department of Pathology, University of Aberdeen, Foresterhill, Aberdeen, AB9 2ZD, Scotland

    Angus W. Thomson BSc(Hons), MSc, PhD, DSc, MRCPath, FIBiol (Reader in Immunology) (Reader in Immunology)

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Kay, J.E. (1989). Inhibitory effects of cyclosporin A on lymphocyte activation. In: Thomson, A.W. (eds) Cyclosporin. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-0859-8_1

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  • DOI: https://doi.org/10.1007/978-94-009-0859-8_1

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