1932

Abstract

Autoimmunity and the pathogenesis of autoimmune diseases were a major focus of the Walter and Eliza Hall Institute, where I started my research career. After my initial studies on immune cell culture and immune regulation, I returned to an analysis of the pathogenesis of human autoimmunity in London. Linking upregulated antigen presentation to autoimmunity led to an investigation of the role of cytokines in rheumatoid arthritis (RA), in collaboration with Ravinder Maini. These experiments defined the concept of a TNF-dependent cytokine cascade driving the manifestations of RA, which led to successful clinical trials of anti-TNF monoclonal antibody in RA patients, heralding a major change in medical practice. This success was made possible by enthusiastic support from many laboratory and clinical colleagues and taught us that cytokines are important rate-limiting steps and hence good therapeutic targets. My current scientific challenge is exploring the hypothesis of whether all major medical needs can be approached via cytokine blockade.

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2009-04-23
2024-06-14
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Literature Cited

  1. Mishell RI, Dutton RW. 1.  1966. Immunization of normal mouse spleen cell suspensions in vitro. Science 153:1004–6 [Google Scholar]
  2. Marbrook J. 2.  1967. Primary immune response in cultures of spleen cells. Lancet 2:1279–81 [Google Scholar]
  3. Diener E, Armstrong WD. 3.  1967. Induction of antibody formation and tolerance in vitro to a purified protein antigen. Lancet 2:1281–85 [Google Scholar]
  4. Ada GL, Nossal GJ. 4.  1987. The clonal-selection theory. Sci. Am. 257:62–69 [Google Scholar]
  5. Diener E. 5.  1968. A new method for the enumeration of single antibody-producing cells. J. Immunol. 100:1062–70 [Google Scholar]
  6. Jerne NK, Nordin AA. 6.  1963. Plaque formation in agar by single antibody-producing cells. Science 140:405 [Google Scholar]
  7. Feldmann M. 7.  1971. Induction of immunity and tolerance to the dinitrophenyl determinant in vitro. Nat. New Biol. 231:21–23 [Google Scholar]
  8. Lennon V, Feldmann M. 8.  1972. The detection of autoantibody-forming cells. I. An assay for plaque-forming cells to the basic protein of myelin in guinea-pigs. Int. Arch. Allergy Appl. Immunol. 42:627–40 [Google Scholar]
  9. Miller JF, Mitchell GF. 9.  1968. Cell to cell interaction in the immune response. I. Hemolysin-forming cells in neonatally thymectomized mice reconstituted with thymus or thoracic duct lymphocytes. J. Exp. Med. 128:801–20 [Google Scholar]
  10. Mitchell GF, Miller JF. 10.  1968. Cell to cell interaction in the immune response. II. The source of hemolysin-forming cells in irradiated mice given bone marrow and thymus or thoracic duct lymphocytes. J. Exp. Med. 128:821–37 [Google Scholar]
  11. Nossal GJ, Cunningham A, Mitchell GF, Miller JF. 11.  1968. Cell to cell interaction in the immune response. 3. Chromosomal marker analysis of single antibody-forming cells in reconstituted, irradiated, or thymectomized mice. J. Exp. Med. 128:839–53 [Google Scholar]
  12. Roitt IM, Greaves MF, Torrigiani G, Brostoff J, Playfair JH. 12.  1969. The cellular basis of immunological responses. A synthesis of some current views. Lancet 2:367–71 [Google Scholar]
  13. Greaves MF, Roitt IM, Rose ME. 13.  1968. Effect of bursectomy and thymectomy on the responses of chicken peripheral blood lymphocytes to phytohaemagglutinin. Nature 220:293–95 [Google Scholar]
  14. Feldmann M, Basten A. 14.  1971. The relationship between antigenic structure and the requirement for thymus-derived cells in the immune response. J. Exp. Med. 134:103–19 [Google Scholar]
  15. Feldmann M, Basten A. 15.  1972. Cell interactions in the immune response in vitro. 3. Specific collaboration across a cell impermeable membrane. J. Exp. Med. 136:49–67 [Google Scholar]
  16. Feldmann M, Basten A. 16.  1972. Specific collaboration between T and B lymphocytes across a cell impermeable membrane in vitro. Nat. New Biol. 237:13–15 [Google Scholar]
  17. Schimpl A, Wecker E. 17.  1972. Replacement of T-cell function by a T-cell product. Nat. New Biol. 237:15–17 [Google Scholar]
  18. Feldmann M. 18.  1972. Cell interaction in the immune response in vitro. II. The requirement for macrophages in lymphoid cell collaboration. J. Exp. Med. 135:1049–58 [Google Scholar]
  19. Lennon V, Feldmann M, Crawford M. 19.  1972. The detection of autoantibody-forming cells. II. Cells in lymph nodes and central nervous system containing antibody to myelin basic protein. Int. Arch. Allergy Appl. Immunol. 43:749–58 [Google Scholar]
  20. Hanafusa T, Pujol-Borrell R, Chiovato L, Russell RC, Doniach D, Bottazzo GF. 20.  1983. Aberrant expression of HLA-DR antigen on thyrocytes in Graves’ disease: relevance for autoimmunity. Lancet 2:1111–15 [Google Scholar]
  21. Klareskog L, Forsum U, Scheynius A, Kabelitz D, Wigzell H. 21.  1982. Evidence in support of a self-perpetuating HLA-DR-dependent delayed-type cell reaction in rheumatoid arthritis. Proc. Natl. Acad. Sci. USA 79:3632–36 [Google Scholar]
  22. Bussard AE, Lurie M. 22.  1967. Primary antibody response in vitro in peritoneal cells. J. Exp. Med. 125:873–92 [Google Scholar]
  23. Schrader JW, Feldmann M. 23.  1973. The mechanism of antigenic competition. I. The macrophage as a site of a reversible block of T-B lymphocyte collaboration. Eur. J. Immunol. 3:711–17 [Google Scholar]
  24. Wagner H, Feldmann M. 24.  1972. Cell-mediated immune response in vitro. I. A new in vitro system for the generation of cell-mediated cytotoxic activity. Cell. Immunol. 3:405–20 [Google Scholar]
  25. Wunderlich JR, Canty TG. 25.  1970. Cell mediated immunity induced in vitro. Nature 228:62–63 [Google Scholar]
  26. Mitchison NA. 26.  1971. The carrier effect in the secondary response to hapten-protein conjugates. I. Measurement of the effect with transferred cells and objections to the local environment hypothesis. Eur. J. Immunol. 1:10–17 [Google Scholar]
  27. Raff MC, Nase S, Mitchison NA. 27.  1971. Mouse specific bone marrow-derived lymphocyte antigen as a marker for thymus-independent lymphocytes. Nature 230:50–51 [Google Scholar]
  28. Hulett HR, Bonner WA, Sweet RG, Herzenberg LA. 28.  1973. Development and application of a rapid cell sorter. Clin. Chem. 19:813–16 [Google Scholar]
  29. Zinkernagel RM, Doherty PC. 29.  1974. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature 248:701–2 [Google Scholar]
  30. Horton JE, Raisz LG, Simmons HA, Oppenheim JJ, Mergenhagen SE. 30.  1972. Bone resorbing activity in supernatant fluid from cultured human peripheral blood leukocytes. Science 177:793–95 [Google Scholar]
  31. Nathan CF, Remold HG, David JR. 31.  1973. Characterization of a lymphocyte factor which alters macrophage functions. J. Exp. Med. 137:275–90 [Google Scholar]
  32. Gillis S, Ferm MM, Ou W, Smith KA. 32.  1978. T cell growth factor: parameters of production and a quantitative microassay for activity. J. Immunol. 120:2027–32 [Google Scholar]
  33. Howard M, Farrar J, Hilfiker M, Johnson B, Takatsu K. 33.  et al. 1982. Identification of a T cell-derived B cell growth factor distinct from interleukin 2. J. Exp. Med. 155:914–23 [Google Scholar]
  34. Smith KA, Lachman LB, Oppenheim JJ, Favata MF. 34.  1980. The functional relationship of the interleukins. J. Exp. Med. 151:1551–56 [Google Scholar]
  35. Smith KA, Gilbride KJ, Favata MF. 35.  1980. Lymphocyte activating factor promotes T cell growth factor production by cloned murine lymphoma cells. Nature 287:853–55 [Google Scholar]
  36. Oppenheim JJ, Gery I. 36.  1982. Interleukin 1 is more than an interleukin. Immunol. Today 3:113–19 [Google Scholar]
  37. 37. Letter to the Editor 1979. Revised nomenclature for antigen-non specific T cell proliferation and helper factors. J. Immunol. 123:2928–29 [Google Scholar]
  38. Tonegawa S, Brack C, Hozumi N, Schuller R. 38.  1977. Cloning of an immunoglobulin variable region gene from mouse embryo. Proc. Natl. Acad. Sci. USA 74:3518–22 [Google Scholar]
  39. Gresser I. 39.  1972. Antitumor effects of interferon. Adv. Cancer Res. 16:97–140 [Google Scholar]
  40. Taniguchi T, Fujii-Kuriyama Y, Muramatsu M. 40.  1980. Molecular cloning of human interferon cDNA. Proc. Natl. Acad. Sci. USA 77:4003–6 [Google Scholar]
  41. Goeddel DV, Shepard HM, Yelverton E, Leung D, Crea R. 41.  et al. 1980. Synthesis of human fibroblast interferon by E. coli. Nucleic Acids Res. 8:4057–74 [Google Scholar]
  42. Nagata S, Taira H, Hall A, Johnsrud L, Streuli M. 42.  et al. 1980. Synthesis in E. coli of a polypeptide with human leukocyte interferon activity. Nature 284:316–20 [Google Scholar]
  43. Auron PE, Webb AC, Rosenwasser LJ, Mucci SF, Rich A. 43.  et al. 1984. Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proc. Nat. Acad. Sci. USA 81:7907–11 [Google Scholar]
  44. Taniguchi T, Matsui H, Fujita T, Takaoka C, Kashima N. 44.  et al. 1983. Structure and expression of a cloned cDNA for human interleukin-2. Nature 203:305–10 [Google Scholar]
  45. Paul WE, Ohara J. 45.  1987. B-cell stimulatory factor-1/interleukin 4. Annu. Rev. Immunol. 5:429–59 [Google Scholar]
  46. Pennica D, Hayflick JS, Bringman TS, Palladino MA, Goeddel DV. 46.  1985. Cloning and expression in Escherichia coli of the cDNA for murine tumor necrosis factor. Proc. Natl. Acad. Sci. USA 82:6060–64 [Google Scholar]
  47. Janossy G, Panayi G, Duke O, Bofill M, Poulter LW, Goldstein G. 47.  1981. Rheumatoid arthritis: a disease of T-lymphocyte/macrophage immunoregulation. Lancet 2:839–42 [Google Scholar]
  48. McDevitt HO, Chinitz A. 48.  1969. Genetic control of the antibody response: relationship between immune response and histocompatibility (H-2) type. Science 163:1207–8 [Google Scholar]
  49. Steeg PS, Moore RN, Johnson HM, Oppenheim JJ. 49.  1982. Regulation of murine macrophage Ia antigen expression by a lymphokine with immune interferon activity. J. Exp. Med. 156:1780–93 [Google Scholar]
  50. Bottazzo GF, Pujol-Borrell R, Hanafusa T, Feldmann M. 50.  1983. Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunity. Lancet 2:1115–19 [Google Scholar]
  51. Lamb JR, Eckels DD, Lake P, Woody JN, Green N. 51.  1982. Human T cell clones recognize chemically synthesized peptides of influenza haemagglutinin. Nature 300:66–69 [Google Scholar]
  52. Londei M, Lamb JR, Bottazzo GF, Feldmann M. 52.  1984. Epithelial cells expressing aberrant MHC class II determinants can present antigen to cloned human T cells. Nature 312:639–41 [Google Scholar]
  53. Londei M, Bottazzo GF, Feldmann M. 53.  1985. Human T-cell clones from autoimmune thyroid glands: specific recognition of autologous thyroid cells. Science 228:85–89 [Google Scholar]
  54. McLachlan SM, Rapoport B. 54.  1989. Evidence for a potential common T-cell epitope between human thyroid peroxidase and human thyroglobulin with implications for the pathogenesis of autoimmune thyroid disease. Autoimmunity 5:101–6 [Google Scholar]
  55. Dayan CM, Londei M, Corcoran AE, Grubeck-Loebenstein B, James RF. 55.  et al. 1991. Autoantigen recognition by thyroid-infiltrating T cells in Graves disease. Proc. Natl. Acad. Sci. USA 88:7415–19 [Google Scholar]
  56. Pujol-Borrell R, Todd I, Doshi M, Bottazzo GF, Sutton R. 56.  et al. 1987. HLA class II induction in human islet cells by interferon-γ plus tumour necrosis factor or lymphotoxin. Nature 326:304–6 [Google Scholar]
  57. Sarvetnick N, Liggitt D, Pitts SL, Hansen SE, Stewart TA. 57.  1988. Insulin dependent diabetes mellitus induced in transgenic mice by ectopic expression of class II MHC and interferon-γ. Cell 52:773–82 [Google Scholar]
  58. Buchan G, Barrett K, Turner M, Chantry D, Maini RN, Feldmann M. 58.  1988. Interleukin-1 and tumour necrosis factor mRNA expression in rheumatoid arthritis: prolonged production of IL-1 α. Clin. Exp. Immunol. 73:449–55 [Google Scholar]
  59. Buchan G, Barrett K, Fujita T, Taniguchi T, Maini R, Feldmann M. 59.  1988. Detection of activated T cell products in the rheumatoid joint using cDNA probes to interleukin-2 (IL-2) IL-2 receptor and IFN-γ. Clin. Exp. Immunol. 71:295–301 [Google Scholar]
  60. Palmer DG. 60.  1970. Dispersed cell cultures of rheumatoid synovial membrane. Acta Rheumatol. Scand. 16:261–70 [Google Scholar]
  61. Brennan FM, Chantry D, Jackson A, Maini R, Feldmann M. 61.  1989. Inhibitory effect of TNFα antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet 2:244–47 [Google Scholar]
  62. Haworth C, Brennan FM, Chantry D, Turner M, Maini RN, Feldmann M. 62.  1991. Expression of granulocyte-macrophage colony-stimulating factor in rheumatoid arthritis: regulation by tumor necrosis factor-α. Eur. J. Immunol. 21:2575–79 [Google Scholar]
  63. Butler DM, Feldmann M, Di Padova F, Brennan FM. 63.  1994. p55 and p75 tumor necrosis factor receptors are expressed and mediate common functions in synovial fibroblasts and other fibroblasts. Eur. Cytokine Netw. 5:441–48 [Google Scholar]
  64. Feldmann M, Brennan FM, Maini RN. 64.  1996. Role of cytokines in rheumatoid arthritis. Annu. Rev. Immunol. 14:397–440 [Google Scholar]
  65. Williams RO, Feldmann M, Maini RN. 65.  1992. Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. Proc. Nat. Acad. Sci. USA 89:9784–88 [Google Scholar]
  66. Thorbecke GJ, Shah R, Leu CH, Kuruvilla AP, Hardison AM, Palladino MA. 66.  1992. Involvement of endogenous tumor necrosis factor α and transforming growth factor β during induction of collagen type II arthritis in mice. Proc. Natl. Acad. Sci. USA 89:7375–79 [Google Scholar]
  67. Piguet PF, Grau GE, Vesin C, Loetscher H, Gentz R, Lesslauer W. 67.  1992. Evolution of collagen arthritis in mice is arrested by treatment with antitumour necrosis factor (TNF) antibody or a recombinant soluble TNF receptor. Immunology 77:510–14 [Google Scholar]
  68. Maini RN, Bryceson AD, Wolstencroft RA, Dumonde DC. 68.  1969. Lymphocyte mitogenic factor in man. Nature 224:43–44 [Google Scholar]
  69. Carter P, Presta L, Gorman CM, Ridgway JB, Henner D. 69.  et al. 1992. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc. Nat. Acad. Sci. USA 89:4285–89 [Google Scholar]
  70. Hudziak RM, Lewis GD, Winget M, Fendly BM, Shepard HM. 70.  1989. p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor. Mol. Cell. Biol. 9:1165–72 [Google Scholar]
  71. Siegel SA, Shealy DJ, Nakada MT, Le J, Woulfe DS. 71.  et al. 1995. The mouse/human chimeric monoclonal antibody cA2 neutralizes TNF in vitro and protects transgenic mice from cachexia and TNF lethality in vivo. Cytokine 7:15–25 [Google Scholar]
  72. Beutler B, Milsark IW, Cerami AC. 72.  1985. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 229:869–71 [Google Scholar]
  73. Elliott MJ, Maini RN, Feldmann M, Long-Fox A, Charles P. 73.  et al. 1993. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor α. Arthritis Rheum. 36:1681–90 [Google Scholar]
  74. Tracey KJ, Fong Y, Hesse DG, Manogue KR, Lee AT. 74.  et al. 1987. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature 330:662–64 [Google Scholar]
  75. Elliott MJ, Maini RN, Feldmann M, Long-Fox A, Charles P. 75.  et al. 1994. Repeated therapy with monoclonal antibody to tumour necrosis factor α (cA2) in patients with rheumatoid arthritis. Lancet 344:1125–27 [Google Scholar]
  76. Elliott MJ, Maini RN, Feldmann M, Kalden JR, Antoni C. 76.  et al. 1994. Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor α (cA2) versus placebo in rheumatoid arthritis. Lancet 344:1105–10 [Google Scholar]
  77. Charles P, Elliott MJ, Davis D, Potter A, Kalden JR. 77.  et al. 1999. Regulation of cytokines, cytokine inhibitors, and acute-phase proteins following anti-TNF-α therapy in rheumatoid arthritis. J. Immunol. 163:1521–28 [Google Scholar]
  78. Davis D, Charles PJ, Potter A, Feldmann M, Maini RN, Elliott MJ. 78.  1997. Anaemia of chronic disease in rheumatoid arthritis: in vivo effects of tumour necrosis factor α blockade. Br. J. Rheumatol. 36:950–56 [Google Scholar]
  79. Dixon WG, Watson KD, Lunt M, Hyrich KL, Silman AJ, Symmons DP. 79.  2007. Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis who respond to antitumor necrosis factor α therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum. 56:2905–12 [Google Scholar]
  80. Hyrich KL, Watson KD, Isenberg DA, Symmons DP. 80.  2008. The British Society for Rheumatology Biologics Register: 6 years on. Rheumatology. 47:1441–43 [Google Scholar]
  81. Askling J, Fored CM, Geborek P, Jacobsson LT, van Vollenhoven R. 81.  et al. 2006. Swedish registers to examine drug safety and clinical issues in RA. Ann. Rheum. Dis. 65:707–12 [Google Scholar]
  82. Jacobsson LT, Turesson C, Gulfe A, Kapetanovic MC, Petersson IF. 82.  et al. 2005. Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis. J. Rheumatol. 32:1213–18 [Google Scholar]
  83. Paleolog EM, Hunt M, Elliott MJ, Feldmann M, Maini RN, Woody JN. 83.  1996. Deactivation of vascular endothelium by monoclonal antitumor necrosis factor α antibody in rheumatoid arthritis. Arthritis Rheum. 39:1082–91 [Google Scholar]
  84. Taylor PC, Peters AM, Paleolog E, Chapman PT, Elliott MJ. 84.  et al. 2000. Reduction of chemokine levels and leukocyte traffic to joints by tumor necrosis factor α blockade in patients with rheumatoid arthritis. Arthritis Rheum. 43:38–47 [Google Scholar]
  85. Brennan FM, Browne KA, Green PA, Jaspar JM, Maini RN, Feldmann M. 85.  1997. Reduction of serum matrix metalloproteinase 1 and matrix metalloproteinase 3 in rheumatoid arthritis patients following anti-tumour necrosis factor-α (cA2) therapy. Br. J. Rheumatol. 36:643–50 [Google Scholar]
  86. Paleolog EM, Young S, Stark AC, McCloskey RV, Feldmann M, Maini RN. 86.  1998. Modulation of angiogenic vascular endothelial growth factor by tumor necrosis factor α and interleukin-1 in rheumatoid arthritis. Arthritis Rheum. 41:1258–65 [Google Scholar]
  87. Ballara S, Taylor PC, Reusch P, Marme D, Feldmann M. 87.  et al. 2001. Raised serum vascular endothelial growth factor levels are associated with destructive change inflammatory arthritis. Arthritis Rheum. 44:2055–64 [Google Scholar]
  88. Keffer J, Probert L, Cazlaris H, Georgopoulos S, Kaslaris E. 88.  et al. 1991. Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J. 10:4025–31 [Google Scholar]
  89. Kontoyiannis D, Pasparakis M, Pizarro TT, Cominelli F, Kollias G. 89.  1999. Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies. Immunity 10:387–98 [Google Scholar]
  90. Williams RO, Mauri C, Mason LJ, Marinova-Mutafchieva L, Ross SE. 90.  et al. 1998. Therapeutic actions of cyclosporine and antitumor necrosis factor α in collagen-induced arthritis and the effect of combination therapy. Arthritis Rheum. 41:1806–12 [Google Scholar]
  91. Williams RO, Mason LJ, Feldmann M, Maini RN. 91.  1994. Synergy between anti-CD4 and antitumor necrosis factor in the amelioration of established collagen-induced arthritis. Proc. Natl. Acad. Sci. USA 91:2762–66 [Google Scholar]
  92. Webb LM, Walmsley MJ, Feldmann M. 92.  1996. Prevention and amelioration of collagen-induced arthritis by blockade of the CD28 costimulatory pathway: requirement for both B7-1 and B7-2. Eur. J. Immunol. 26:2320–28 [Google Scholar]
  93. Weinblatt ME, Trentham DE, Fraser PA, Holdsworth DE, Falchuk KR. 93.  et al. 1988. Long term prospective trial of low-dose methotrexate in rheumatoid arthritis. Arthritis Rheum. 31:167–75 [Google Scholar]
  94. Weinblatt ME, Maier AL, Fraser PA, Coblyn JS. 94.  1998. Longterm prospective study of methotrexate in rheumatoid arthritis: conclusion after 132 months of therapy. J. Rheumatol. 25:238–42 [Google Scholar]
  95. Gerards AH, de Lathouder S, de Groot ER, Dijkmans BA, Aarden LA. 95.  2003. Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patients with rheumatoid arthritis. Rheumatology 42:1189–96 [Google Scholar]
  96. Genestier L, Paillot R, Fournel S, Ferraro C, Miossec P, Revillard JP. 96.  1998. Immunosuppressive properties of methotrexate: apoptosis and clonal deletion of activated peripheral T cells. J. Clin. Invest. 102:322–28 [Google Scholar]
  97. Maini RN, Breedveld FC, Kalden JR, Smolen JS, Davis D. 97.  et al. 1998. Therapeutic efficacy of multiple intravenous infusions of antitumor necrosis factor α monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum. 41:1552–63 [Google Scholar]
  98. Maini R, St Clair EW, Breedveld F, Furst D, Kalden J. 98.  et al. 1999. Infliximab (chimeric antitumour necrosis factor α monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet 354:1932–39 [Google Scholar]
  99. Weinblatt ME, Keystone EC, Furst DE, Moreland LW, Weisman MH. 99.  et al. 2003. Adalimumab, a fully human antitumor necrosis factor α monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum. 48:35–45 [Google Scholar]
  100. Klareskog L, Van Der Heijde D, de Jager P, Gough A, Kalden J. 100.  et al. 2004. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 363:675–81 [Google Scholar]
  101. Derkx B, Taminiau J, Radema S, Stronkhorst A, Wortel C. 101.  et al. 1993. Tumor necrosis factor antibody treatment in Crohn's disease. Lancet 342:173–74 [Google Scholar]
  102. Howard JG, Christie GH, Courtenay BM, Leuchars E, Davies AJ. 102.  1971. Studies on immunological paralysis. VI. Thymic-independence of tolerance and immunity to type 3 pneumococcal polysaccharide. Cell. Immunol. 2:614–26 [Google Scholar]
  103. Feldmann M. 103.  1972. Induction of immunity and tolerance in vitro by hapten protein conjugates. I. The relationship between the degree of hapten conjugation and the immunogenicity of dinitrophenylated polymerized flagellin. J. Exp. Med. 135:735–53 [Google Scholar]
  104. Smith C, Wortel C, Dixon W, Ziegler E. 104.  1991. Monoclonal antibody HA-1A for gram-negative shock. Lancet 338:695–96 [Google Scholar]
  105. Katsikis MP, Harris G, Page T, Paleolog E, Feldmann M. 105.  et al. 1993. Antilipid A monoclonal antibody HA-1A: immune complex clearance of endotoxin reduces TNF-α, IL-1b and IL-6 production. Cytokine 5:348–53 [Google Scholar]
  106. Medawar P. 106.  1967. The Art of the Soluble London: Methuen [Google Scholar]
  107. Kohler G, Milstein C. 107.  1976. Derivation of specific antibody-producing tissue culture and tumor lines by cell fusion. Eur. J. Immunol. 6:511–19 [Google Scholar]
  108. Feldmann M, Lamb JR, Woody JN. 108.  1985. Human T Cell Clones Clifton, NJ: Humana [Google Scholar]
  109. Feldmann M, McMichael A. 109.  1986. Regulation of Immune Gene Expression Clifton, NJ: Humana [Google Scholar]
  110. Feldmann M, Maini RN, Woody JN. 110.  1989. T Cell Activation in Health and Disease London: Acad. Ltd. [Google Scholar]
  111. Feldmann M, Maini RN. 111.  2001. Anti-TNFα therapy or rheumatoid arthritis: What have we learned?. Annu. Rev. Immunol. 19:163–96 [Google Scholar]
  112. Chatenoud L, Ferran C, Legendre C, Thouard I, Merite S. 112.  et al. 1990. In vivo cell activation following OKT3 administration. Systemic cytokine release and modulation by corticosteroids. Transplantation 49:697–702 [Google Scholar]
  113. Maloney DG, Grillo-Lopez AJ, White CA, Bodkin D, Schilder RJ. 113.  et al. 1997. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood 90:2188–95 [Google Scholar]
  114. Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P. 114.  et al. 2004. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N. Engl. J. Med. 350:2572–81 [Google Scholar]
  115. Campion GV, Lebsack ME, Lookabaugh J, Gordon G, Catalano M. 115.  1996. Dose-range and dose-frequency study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis. The IL-1Ra Arthritis Study Group. Arthritis Rheum. 39:1092–101 [Google Scholar]
  116. Nishimoto N, Kishimoto T. 116.  2006. Interleukin 6: from bench to bedside. Nat. Clin. Pract. Rheumatol. 2:619–26 [Google Scholar]
  117. Maini RN, Taylor PC, Szechinski J, Pavelka K, Broll J. 117.  et al. 2006. Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum. 54:2817–29 [Google Scholar]
  118. Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B. 118.  et al. 2008. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone 43:222–29 [Google Scholar]
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