Antipurines and Purine Metabolism

  • G. Wolberg
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 85)


The study of the involvement of purines in lymphocyte function has been highlighted by two dramatic and unrelated discoveries. The first, the discovery in 1958 that 6-mercaptopurine (6-MP) had marked immunosuppressive properties (Schwartz et al. 1958), was followed by the wide use of its S-substituted analog, azathioprine (Aza), to prevent rejection of kidney transplants (Murray et al. 1967). The second, the discovery by Giblett that deficiencies in either of two enzymes of the purine catabolic pathway, adenosine deaminase (ADA) (Giblett et al. 1972) or purine nucleoside phosphorylase (PNP) (Giblett et al. 1975), were associated with immunodeficiency disease, led to many studies involving purine metabolism in lymphocytes as well as the modulation of lymphocyte function by purines.


Adenosine Deaminase Natural Killer Cell Activity Natural Killer Activity Purine Metabolism Purine Nucleoside Phosphorylase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Agarwal RP, Crabtree GW, Parks RE Jr, Nelson JA, Keightley R, Parkman R, Rosen FS, Stern RC, Polmar SH (1976) Purine nucleoside metabolism in the erythrocytes of patients with adenosine deaminase deficiency and severe combined immunodeficiency. J Clin Invest 57: 1025–1035PubMedGoogle Scholar
  2. Allison AC, Hovi T, Watts RWE, Webster ADB (1975) Immunological observations on patients with Lesch-Nyhan syndrome and on the role of de-novo purine synthesis in lymphocyte transformation. Lancet II: 1179–1183Google Scholar
  3. Al-Safi SA, Maddocks JL (1984) Azathioprine and 6-mercaptopurine (6-MP) suppress the human mixed lymphocyte reaction (MLR) by different mechanisms. Br J Clin Pharmacol 17: 417–422PubMedGoogle Scholar
  4. Bach JF, Dardenne M, Fournier C (1969) In vitro evaluation of immunosuppressive drugs. Nature 222: 998–999PubMedGoogle Scholar
  5. Breter HJ (1985) The quantitative determination of metabolites of 6-mercaptopurine in biological materials. VI. Evidence for posttranscriptional modification of 6-thioguanosine residues in RNA from L5178Y cells treated with 6-mercaptopurine. Biochim Biophys Acta 825: 39–44PubMedGoogle Scholar
  6. Brockman RW (1960) A mechanism of resistance to 6-mercaptopurine: metabolism of hypoxanthine and 6-mercaptopurine by sensitive and resistant neoplasms. Cancer Res 20: 643–653PubMedGoogle Scholar
  7. Brockman RW (1965) Resistance to purine antagonists in experimental leukemia systems. Cancer Res 25: 1596–1605PubMedGoogle Scholar
  8. Brogan M, Hiserodt J, Oliver M, Stevens R, Korelitz B, Targon S (1985) The effect of 6mercaptopurine on natural killer-cell activities in Crohn’s disease. J Clin Immunol 5: 204–211PubMedGoogle Scholar
  9. Brown TE, Ahmed A, Filo RS, Knudsen RC, Sell KW (1976) The immunosuppressive mechanism of azathioprine. I. In vitro effect on lymphocyte function in the baboon. Transplantation 21: 27–35PubMedGoogle Scholar
  10. Campbell AC, Skinner JM, Maclennan ICM, Hersey P, Waller CA, Wood J, Jewell DP, Truelove SC (1976) Immunosuppression in the treatment of inflammatory bowel disease. II. The effects of azathioprine on lymphoid cell populations in a double blind trial in ulcerative colitis. Clin Exp Immunol 24: 249–258PubMedGoogle Scholar
  11. Calne RY, Alexandre GPJ, Murray JE (1962) A study of the effects of drugs in prolonging survival of homologous renal transplants in dogs. Ann NY Acad Sci 99: 743–761PubMedGoogle Scholar
  12. Carson DA, Kaye J, Seegmiller JE (1977) Lymphospecific toxicity in adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency: possible role of nucleoside kinase(s). Proc Natl Acad Sci USA 74: 5677–5681PubMedGoogle Scholar
  13. Carson DA, Kaye J, Seegmiller JE (1978) Differential sensitivity of human leukemic T cell lines and B cell lines to growth inhibition by deoxyadenosine. J Immunol 121: 1726–1731PubMedGoogle Scholar
  14. Carson DA, Kaye J, Matsumoto S, Seegmiller JE, Thompson L (1979) Biochemical basis for the enhanced toxicity of deoxyribonucleosides toward malignant human T cell lines. Proc Natl Acad Sci USA 76: 2430–2433PubMedGoogle Scholar
  15. Carson DA, Kaye J, Wasson DB (1981) The potential importance of soluble deoxynucleotidase activity in mediating deoxyadenosine toxicity in human lymphoblasts. J Immunol 126: 348–352PubMedGoogle Scholar
  16. Chalmers AH, Knight PR, Atkinson MR (1967) Conversion of azathioprine into mercaptopurine and mercaptoimidazole derivatives in vitro and during immunosuppressive therapy. Aust J Exp Biol Med Sci 45: 681–691PubMedGoogle Scholar
  17. Chatenoud L, Kreis H, Jungers P, Bach JF (1981) The effect of immunosuppressive agents on T-cell subsets, as evaluated by use of monoclonal anti-T-cell antibodies. Transplant Proc 13: 1651–1656PubMedGoogle Scholar
  18. Chen SH, Ochs HD, Scott CR, Giblett ER, Tingle Al (1978) Adenosine deaminase deficiency: disappearance of adenine deoxynucleotides from a patient’s erythrocytes after successful marrow transplantation. J Clin Invest 62: 1386–1389PubMedGoogle Scholar
  19. Claman HN, Chaperon EA, Triplett RF (1966) Thymus-marrow cell combinations. Synergism in antibody production. Proc Soc Exp Biol Med 122: 1167–1171PubMedGoogle Scholar
  20. Cohen A, Doyle D, Martin DW Jr, Ammann AJ (1976) Abnormal purine metabolism and purine overproduction in a patient deficient in purine nucleoside phosphorylase. N Engl J Med 295: 1449–1454PubMedGoogle Scholar
  21. Cohen A, Gudas LJ, Ammann AJ, Staal GEJ, Martin DW Jr (1978a) Deoxyguanosine triphosphate as a possible toxic metabolite in the immunodeficiency associated with purine nucleoside phosphorylase deficiency. J Clin Invest 61:1405–1409Google Scholar
  22. Cohen A, Hirschhorn R, Horowitz SD, Rubinstein A, Polmar SH, Hong R, Martin DW Jr (1978b) Deoxyadenosine triphosphate as a potentially toxic metabolite in adenosine deaminase deficiency. Proc Natl Acad Sci USA 75:472–476Google Scholar
  23. Coleman MS, Donofrio J, Hutton JJ, Hahn L, Daoud A, Lampkin B, Dyminski J (1978) Identification and quantitation of adenine deoxynucleotides in erythrocytes of a patient with adenosine deaminase deficiency and severe combined immunodeficiency. J Biol Chem 253: 1619–1626PubMedGoogle Scholar
  24. Cosimi AB, Colvin RB, Burton RC, Rubin RH, Goldstein G, Kung PC, Hansen WP, Delmonico FL, Russell PS (1981) Use of monoclonal antibodies to T-cell subsets for immunologic monitoring and treatment in recipients of renal allografts. N Engl J Med 305: 308–314PubMedGoogle Scholar
  25. Crawford DH, Edwards JMB, Sweny P, Hoffbrand AV, Janossy G (1981) Studies on longterm T-cell-mediated immunity to Epstein-Barr virus in immunosuppressed renal allo-graft recipients. Int J Cancer 28: 705–709PubMedGoogle Scholar
  26. Dalke AP, Kazmers IS, Kelley WN (1984) Hypoxanthine-guanine phosphoribosyltransferase-independent toxicity of azathioprine in human lymphoblasts. Biochem Pharmacol 33: 2692–2695PubMedGoogle Scholar
  27. Davies AJS, Leuchars E, Wallis V, Marchant R, Elliott EV (1967) The failure of thymus-derived cells to produce antibody. Transplantation 5: 222–231Google Scholar
  28. De Landazuri MO, Silva A, Alvarez J, Herberman RB (1979) Evidence that natural cytotoxicity and antibody-dependent cellular cytotoxicity are mediated in humans by the same effector cell populations. J Immunol 123: 252–258PubMedGoogle Scholar
  29. De Miranda P, Beacham LM III, Creagh TH, Elion GB (1973) The metabolic fate of the methylnitroimidazole moiety of azathioprine in the rat. J Pharmacol Exp Ther 187: 588–601PubMedGoogle Scholar
  30. De Miranda P, Beacham LM III, Creagh TH, Elion GB (1975) The metabolic disposition of 14C-azathioprine in the dog. J Pharmacol Exp Ther 195: 50–57PubMedGoogle Scholar
  31. Descamps B, Gagnon R, Van Der Gaag R, Meyer O, Crosnier J (1977) Influence of azathioprine and prednisone in vivo treatment on lymphocyte-dependent antibody-mediated cytotoxicity (LDAC) in 57 human renal allograft recipients. Transplant Proc 9: 981–984PubMedGoogle Scholar
  32. Dimitriu A, Fauci AS (1978) Activation of human B lymphocytes. XI. Differential effects of azathioprine on B lymphocytes and lymphocyte subpopulations regulating B cell function. J Immunol 121: 2335–2339PubMedGoogle Scholar
  33. Donofrio J, Coleman MS, Hutton JJ, Daoud A, Lampkin B, Dyminski J (1978) Overproduction of adenine deoxynucleosides and deoxynucleotides in adenosine deaminase deficiency with severe combined immunodeficiency disease. J Clin Invest 62: 884–887PubMedGoogle Scholar
  34. Duclos H, Maillat MC, Kreis H, Galanaud P (1979) T suppressor cell function impairment in peripheral blood lymphocytes from transplant recipients under azathioprine and corticosteroids. Transplantation 28: 437–438PubMedGoogle Scholar
  35. Duclos H, Maillot MC, Galanaud P (1982) Differential effects of azathioprine on T cells regulating murine B-cell function. Immunology 46: 595–601PubMedGoogle Scholar
  36. Dumble LJ, Macdonald IM, Kincaid-Smith P, Clunie GJ (1981) Enhanced renal allograft survival from azathioprine/steroid modified antibody-dependent cellular cytotoxicity. Proc Eur Dial Transplant Assoc 18: 475–480PubMedGoogle Scholar
  37. Dupont E, Schandene L, Devos R, Lambermont M, Wybran J (1983) Depletion of lymphocytes with membrane markers of helper phenotype: a feature of acute and chronic drug-induced immunosuppression. Clin Exp Immunol 51: 345–350PubMedGoogle Scholar
  38. Dupont E, Vandercruys M, Wybran J (1984) Deficient natural killer function in patients receiving immunosuppressive drugs: analysis at the cellular level. Cell Immunol 88: 85–95PubMedGoogle Scholar
  39. Edwards NL (1985) Immunodeficiencies associated with errors in purine metabolism. Med Clin North Am 69: 505–518PubMedGoogle Scholar
  40. Edwards NL, Fox IH (1984) Disorders associated with purine and pyrimidine metabolism. Spec Top Endocrinol Metab 6: 95–140PubMedGoogle Scholar
  41. Elion GB (1968) Discussion. In: Miescher PA, Grabar P (eds) 5th International symposium on immuno pathology. Grune and Stratton, NY, pp 399–401Google Scholar
  42. Elion GB (1977) Immunosuppressive agents. Transplant Proc 9: 975–979PubMedGoogle Scholar
  43. Elion GB, Hitchings GH (1975) Azathioprine. In: Sartorelli AC, Johns DG (eds) Handbook of experimental pharmacology, vol 38. Springer, New York, pp 404–425Google Scholar
  44. Elion GB, Benezra FM, Carrington LO, Strelitz RA (1970) Metabolic fate of 14C-azathioprine. Fed Proc 29: 607Google Scholar
  45. Fox RM, Piddington SK, Tripp EH, Tattersall MHN (1981) Ecto-adenosine triphosphatase deficiency in cultured human T and null leukemic lymphocytes. A biochemical basis for thymidine sensitivity. J Clin Invest 68: 544–552PubMedGoogle Scholar
  46. Frazer IH, Mackay IR (1982) T lymphocyte subpopulations defined by two sets of monoclonal antibodies in chronic active hepatitis and systemic lupus erythematosus. Clin Exp Immunol 50: 107–114PubMedGoogle Scholar
  47. Galanaud P, Crevon MC, Dormont J (1975) Effect of azathioprine on in vitro antibody response. Differential effect of B cells involved in thymus-dependent and independent responses. Clin Exp Immunol 22: 139–152PubMedGoogle Scholar
  48. Galanaud P, Crevon MC, Erard D, Wallon C, Dormont J (1976) Two processes for B-cell triggering by T-independent antigens as evidenced by the effect of azathioprine. Cell Immunol 22: 83–92PubMedGoogle Scholar
  49. Gershon RK, Kondo K (1970) Cell interactions in the induction of tolerance: the role of thymic lymphocytes. Immunology 18: 723–737PubMedGoogle Scholar
  50. Giblett ER, Anderson JE, Cohen F, Pollara B, Meuwissen HJ (1972) Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity. Lancet 11: 1067–1069Google Scholar
  51. Giblett ER, Ammann AJ, Wara DW, Sandman R, Diamond LK (1975) Nucleoside-phosphorylase deficiency in a child with severely defective T-cell immunity and normal B-cell immunity. Lancet 1: 1010–1013PubMedGoogle Scholar
  52. Glick B, Chang TS, Jaap RG (1956) The bursa of Fabricius and antibody production. Poult Sci 35: 224–225Google Scholar
  53. Goday A, Webster DR, Simmonds HA (1982) Nucleotide levels in peripheral blood mononuclear cells in immunodeficient children: problems of measurement. J Clin Chem Clin Biochem 20: 370Google Scholar
  54. Good RA, Dalmasso AP, Martinez C, Archer OK, Pierce JC, Papermaster BW (1962) The role of the thymus in development of immunologic capacity in rabbits and mice. J Exp Med 116: 773–796PubMedGoogle Scholar
  55. Górski A, Korczak-Kowalska G, Nowaczyk M, Paczek L, Gaciong Z (1983) The effect of azathioprine on terminal differentiation of human B lymphocytes. Immunopharmacology 6: 259–266PubMedGoogle Scholar
  56. Green H, Chan TS (1973) Pyrimidine starvation induced by adenosine in fibroblasts and lymphoid cells: role of adenosine deaminase. Science 182: 836–837PubMedGoogle Scholar
  57. Gui XE, Rinaldo CR Jr, Ho M (1983) Natural killer cell activity in renal transplant recipients receiving cyclosporine. Infect Immun 41: 965–970PubMedGoogle Scholar
  58. Guillou PJ, Hegarty J, Ramsden C, Davison AM, Will EJ, Giles GR (1982) Changes in human natural killer activity early and late after renal transplantation using conventional immunosuppression. Transplantation 33: 414–421PubMedGoogle Scholar
  59. Herberman RB (1982) Natural killer cells and their possible relevance to transplantation biology. Transplantation 34: 1–7PubMedGoogle Scholar
  60. Herberman RB, Nunn ME, Lavrin DH (1975) Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. I. Distribution of reactivity and specificity. Int J Cancer 16: 216–229PubMedGoogle Scholar
  61. Hershfield MS (1979) Apparent suicide inactivation of human lymphoblast S-adenosylhomocysteine hydrolase by 2’-deoxyadenosine and adenine arabinoside. J Biol Chem 254: 22–25PubMedGoogle Scholar
  62. Hirschhorn R (1977) Adenosine deaminase deficiency and immunodeficiencies. Fed Proc 36: 2166–2170PubMedGoogle Scholar
  63. Hirschhorn R, Ratech H (1983) Genetic deficiencies of adenosine deaminase and purine nucleoside phosphorylase and their implications for therapy of leukemias. Curr Top Hematol 4: 1–35PubMedGoogle Scholar
  64. Hirschhorn R, Sela E (1977) Adenosine deaminase and immunodeficiency: an in vitro model. Cell Immunol 32: 350–360PubMedGoogle Scholar
  65. Hyslop RM, Jardine I (1981) Metabolism of 6-thiopurines. II. Covalent binding of a 6-thiopurine metabolite to mammalian tissue protein in vivo. J Pharmacol Exp Ther 218: 629–635PubMedGoogle Scholar
  66. Kazmers IS, Mitchell BS, Dadonna PE, Wotring LL, Townsend LB, Kelley WN (1981) Inhibition of purine nucleoside phosphorylase by 8-aminoguanosine: selective toxicity for T lymphoblasts. Science 214: 1137–1139PubMedGoogle Scholar
  67. Kazmers IS, Daddona PE, Dalke AP, Kelley WN (1983) Effect of immunosuppressive agents on human T and B lymphoblasts. Biochem Pharmacol 32: 805–810PubMedGoogle Scholar
  68. Kelley WN, Rosenbloom FM, Seegmiller JE (1967) The effects of azathioprine (Imuran) on purine synthesis in clinical disorders of purine metabolism. J Clin Invest 46: 1518–1529PubMedGoogle Scholar
  69. Kelly AP, Schooley RT, Rubin RH, Hirsch MS (1984) Effect of interferon alpha on natural killer cell cytotoxicity in kidney transplant recipients. Clin Immunol Immunopathol 32: 20–28PubMedGoogle Scholar
  70. Keown PA, Stiller CR, Muirhead N, Hellstrom A, Coles R, Howson W (1984) Cyclosporine inhibits cytotoxic T lymphocyte generation in vivo in the naive and immunologically primed allograft recipient. Transplant Proc 16: 1462–1463Google Scholar
  71. Kiessling R, Klein E, Wigzell H (1975) Natural killer cells in the mouse I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype. Eur J Immunol 5: 112–117PubMedGoogle Scholar
  72. Kincade PW, Lee G, Scheid MP, Blum MD (1980) Characterization of murine colony-forming B cells. II. Limits to in vitro maturation, Lyb-2 expression, resolution of IgD+ subsets, and further population analysis. J Immunol 124: 947–953PubMedGoogle Scholar
  73. Koren HS, Williams MS (1978) Natural killing and antibody-dependent cellular cytotoxicity are mediated by different mechanisms and by different cells. J Immunol 121: 1956–1960PubMedGoogle Scholar
  74. Kredich NM, Martin DW Jr (1977) Role of S-adenosylhomocysteine in adenosine-mediated toxicity in cultured mouse T lymphoma cells. Cell 12: 931–938PubMedGoogle Scholar
  75. Lipinski M, Tursz T, Kreis H, Finale Y, Amiel JL (1980) Dissociation of natural killer cell activity and antibody-dependent cell-mediated cytotoxicity in kidney allograft recipients receiving high-dose immunosuppressive therapy. Transplantation 29: 214–218PubMedGoogle Scholar
  76. Martin DW Jr, Gelfand EW (1981) Biochemistry of disease of immunodevelopment. Annu Rev Biochem 50: 845–877PubMedGoogle Scholar
  77. Matsumoto SS, Yu J, Yu AL (1983) Inhibition of RNA synthesis by deoxyadenosine plus deoxycoformycin in resting lymphocytes. J Immunol 131: 2762–2766PubMedGoogle Scholar
  78. McGeorge MB, Russell EC, Mohanakumar T (1982) Immunologic evaluation of longterm effects of childhood ALL chemotherapy: analysis of in vitro NK- and K-cell activities of peripheral blood lymphocytes. Am J Hematol 12: 19–27PubMedGoogle Scholar
  79. Medzihradsky JL, Hollowell RP, Elion GB (1981) Differential inhibition by azathioprine and 6-mercaptopurine of specific suppressor T cell generation in mice. J Immunopharmacol 3: 1–16PubMedGoogle Scholar
  80. Medzihradsky JL, Klein C, Elion GB (1982) Differential interference by azathioprine and 6-mercaptopurine with antibody-mediated immunoregulation: synergism of azathioprine and antibody in the control of an immune response. J Immunol 129: 145–149PubMedGoogle Scholar
  81. Miller JFAP (1961) Immunological function of the thymus. Lancet 11: 748–749Google Scholar
  82. Mills GC, Goldblum RM, Newkirk KE, Schmalstieg FC (1978) Urinary excretion of purines, purine nucleosides, and pseudouridine in adenosine deaminase deficiency. Biochem Med 20: 180–199PubMedGoogle Scholar
  83. Minato N, Reid L, Cantor H, Lengyel P, Bloom BR (1980) Mode of regulation of natural killer cell activity by interferon. J Exp Med 152: 124–137PubMedGoogle Scholar
  84. Moore EC, Hurlbert RB (1966) Regulation of mammalian deoxyribonucleotide biosynthesis by nucleotides as activators and inhibitors. J Biol Chem 241: 4802–4809PubMedGoogle Scholar
  85. Moreau JF, Ythier A, Soulillou JP (1981) Natural killer activity in kidney allograft recipients. Transplant Proc 13: 1610–1613PubMedGoogle Scholar
  86. Moreau JF, Soulillou JP, Ythier A, Hegaret A, Fauconnier (1983) Decrease in natural killer cell activity in kidney allograft recipients. Ann Immunol (Inst Pasteur) 134C: 191–205Google Scholar
  87. Murray JE, Merrill JP, Harrison JH, Wilson RE, Dammin GJ (1963) Prolonged survival of human-kidney homografts by immunosuppressive drug therapy. N Engl J Med 268: 1315–1323PubMedGoogle Scholar
  88. Murray JE, Barnes BA, Atkinson J (1967) Fifth report of the human kidney transplant registry. Transplantation 5: 752–774PubMedGoogle Scholar
  89. Nishida Y, Kamatani N, Tanimoto K, Akaoka I (1979) Inhibition of purine nucleoside phosphorylase activity and of T-cell function with allopurinol-riboside. Agents Actions 9: 549–552PubMedGoogle Scholar
  90. Ochs UH, Chen SH, Ochs HD, Osborne WRA, Scott CR (1979) Purine nucleoside phosphorylase deficiency: a molecular model for selective loss of T cell function. J Immunol 122: 2424–2429PubMedGoogle Scholar
  91. Ohnuma T, Arkin H, Minowada J, Holland JF (1978) Differential chemotherapeutic susceptibility of human T-lymphocytes and B-lymphocytes in culture. J Natl Cancer Inst 60: 749–752PubMedGoogle Scholar
  92. Osborne WRA, Scott CR (1983) The metabolism of deoxyguanosine and guanosine in human B and T lymphoblasts. A role for deoxyguanosine kinase activity in the selective T-cell defect associated with purine nucleoside phosphorylase deficiency. Biochem J 214: 711–718PubMedGoogle Scholar
  93. Otterness IG, Chang YH (1976) Comparative study of cyclophosphamide, 6-mercaptopurine, azathioprine and methotrexate. Relative effects on the humoral and the cellular immune response in the mouse. Clin Exp Immunol 26: 346–354PubMedGoogle Scholar
  94. Pedersen BK, Beyer JM, Rasmussen A, Klarlund K, Horslev-Petersen K, Pedersen BN, Helin P (1984) Azathioprine as single drug in the treatment of rheumatoid arthritis induces complete suppression of natural killer cell activity. Acta Pathol Microbiol Immunol Scand [C] 92c: 221–225Google Scholar
  95. Polmar SH (1980) Metabolic aspects of immunodeficiency disease. Semin Hemato 117: 30–43Google Scholar
  96. Polmar SH, Stern RC, Schwartz AL, Wetzler EM, Chase PA, Hirschhorn R (1976) Enzyme replacement therapy for adenosine deaminase deficiency and severe combined immunodeficiency. N Engl J Med 295: 1337–1343PubMedGoogle Scholar
  97. Prince HE, Ettenger RB, Dorey FJ, Fine RN, Fahey JL (1984) Azathioprine suppression of natural killer activity and antibody-dependent cellular cytotoxicity in renal transplant recipients. J Clin Immunol 4: 312–318PubMedGoogle Scholar
  98. Purves EC, Berenbaum MC (1975) Selective suppression of murine antibody-dependent cell-mediated cytotoxicity by azathioprine. Transplantation 19: 274–276PubMedGoogle Scholar
  99. Ramsey KM, Djeu JY, Rook AH (1984) Decreased circulating large granular lymphocytes associated with depressed natural killer cell activity in renal transplant recipients. Transplantation 38: 351–356PubMedGoogle Scholar
  100. Reinherz EL, Kung PC, Goldstein G, Schlossman SF (1979) Separation of functional subsets of human T cells by a monoclonal antibody. Proc Natl Acad Sci USA 76: 4061–4065PubMedGoogle Scholar
  101. Röllinghoff M, Schrader J, Wagner H (1973) Effect of azathioprine and cytosine arabinoside on humoral and cellular immunity in vitro. Clin Exp Immunol 15: 261–269PubMedGoogle Scholar
  102. Sampson D, Grotelueschen C, Kauffman HM Jr (1975) The human splenic suppressor cell. Transplantation 20: 362–367PubMedGoogle Scholar
  103. Schwartz RS, Stack J, Dameshek W (1958) Effect of 6-mercaptopurine on antibody production. Proc Soc Exp Biol Med 99: 164–167PubMedGoogle Scholar
  104. Seto S, Carrera CJ, Kubota M, Wasson DB, Carson DA (1985) Mechanism of deoxyadenosine and 2-chlorodeoxyadenosine toxicity to nondividing human lymphocytes. J Clin Invest 75: 377–383PubMedGoogle Scholar
  105. Shih WWH, Ellison GW, Myers LW, Durkos-Smith D, Fahey JL (1982) Locus of selective depression of human natural killer cells by azathioprine. Clin Immunol Immunopathol 23: 672–681PubMedGoogle Scholar
  106. Sidi Y, Mitchell BS (1984) 2’-Deoxyguanosine toxicity for B and mature T lymphoid cell lines is mediated by guanine ribonucleotide accumulation. J Clin Invest 74:1640–1648PubMedGoogle Scholar
  107. Smith SR, Terminelli C, Kipilman CT, Smith Y (1979) Comparative effects of azathioprine, cyclophosphamide and frentizole on humoral immunity in mice. J Immunopharmacol 1: 455–481PubMedGoogle Scholar
  108. Spaapen LJM, Rijkers GT, Staal GEJ, Rijksen G, Wadman SK, Stoop JW, Zegers BJM (1984) The effect of deoxyguanosine on human lymphocyte function. 1. Analysis of the interference with lymphocyte proliferation in vitro. J Immunol 132: 2311–2317PubMedGoogle Scholar
  109. Spina CA (1984) Azathioprine as an immune modulating drug: clinical applications. Clin Immunol Allergy 4: 415–446Google Scholar
  110. Sweny P, Tidman N (1982) The effect of cyclosporin A on peripheral blood T cell subpopulations in renal allografts. Clin Exp Immunol 47: 445–448PubMedGoogle Scholar
  111. Tedde A, Balis ME, Ikehara S, Pahwa R, Good RA, Trotta PP (1980) Animal model for immune dysfunction associated with adenosine deaminase deficiency. Proc Natl Acad Sci USA 77: 4899–4903PubMedGoogle Scholar
  112. Ten Berge RJ, Schellekens PT, Surachno S, The TH, ten Veen JH, Wilmink JM (1981) The influence of therapy with azathioprine and prednisone on the immune system of kidney transplant recipients. Clin Immunol Immunopathol 21: 20–32PubMedGoogle Scholar
  113. Thelander L, Reichard P (1979) Reduction of ribonucleotides. Annu Rev Biochem 48: 133–158PubMedGoogle Scholar
  114. Tidd DM, Paterson ARP (1974) A biochemical mechanism for the delayed cytotoxic reaction of 6-mercaptopurine. Cancer Res 34: 738–746PubMedGoogle Scholar
  115. Trotter JL, Rodey GE, Gebel HM (1982) Azathioprine decreases suppressor T cells in patients with multiple sclerosis. N Engl J Med 306: 365–366PubMedGoogle Scholar
  116. Ullman B, Gudas LJ, Cohen A, Martin DW Jr (1978) Deoxyadenosine metabolism and cytotoxicity in cultured mouse T lymphoma cells: a model for immunodeficiency disease. Cell 14: 365–375PubMedGoogle Scholar
  117. Van Buren CT, Kerman R, Agostino G, Payne W, Flechner S, Kahan BD (1982) The cellular target of cyclosporin A action in humans. Surgery 92: 167–174PubMedGoogle Scholar
  118. Waltzer WC, Bachvaroff RJ, Anaise D, Rapaport FT (1984) Natural killer activity after renal transplantation. Transplant Proc 16: 1527–1529PubMedGoogle Scholar
  119. Willemot J, Martineau R, DesRosiers C, Kelly S, Létourneau J, Lalanne M (1979) Inhibition of purine nucleoside phosphorylase and mitogen-stimulated transformation in immunocompetent murine spleen cells by formycin B. Life Sci 25: 1215–1222PubMedGoogle Scholar
  120. Wilson DB (1965) Quantitative studies on the behavior of sensitized lymphocytes in vitro II. Inhibitory influence of the immune suppressor, Imuran, on the destructive reaction of sensitized lymphoid cells against homologous target cells. J Exp Med 122: 167–172PubMedGoogle Scholar
  121. Wolberg G, Zimmerman TP, Hiemstra K, Winston M, Chu LC (1975) Adenosine inhibition of lymphocyte-mediated cytolysis: Possible role of cyclic adenosine monophosphate. Science 187: 957–959PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • G. Wolberg

There are no affiliations available

Personalised recommendations