Immunologic Research

, Volume 20, Issue 1, pp 67–78 | Cite as

Murine mercury-induced autoimmunity

A model of chemically related autoimmunity in humans
  • Lee M. Bagenstose
  • Padmini Salgame
  • Marc Monestier


Human exposure to certain compounds or therapeutic drugs can result in the development of an autoimmune syndrome. Mercury (Hg) induced autoimmunity is one of the few animal models in which administration of a chemical induces a specific loss of tolerance to self-antigens. After receiving subtoxic doses of Hg or other heavy metals, susceptible mouse strains rapidly develop highly specific antibodies to nucleolar antigens. In addition, these animals display a general activation of the immune system, especially pronounced for the Th2 subset and a transient glomerulonephritis with immunoglobulin deposits. Like many human autoimmune diseases, this syndrome is associated with the expression of susceptible major histocompatibility complex (MHC) classII genes. In this article, we review the essential features of this model, and we discuss the putative mechanisms by which Hg creates such a severe immune dysfunction.

Key Words

Mercury Heavy metal Cytokines Animal model Autoimmunity Fibrillarin Nucleolus Scleroderma 


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  1. 1.
    Klassen CD: Toxicology. The Basic Science of Poisons, 5th ed. New York, McGraw-Hill, 1996.Google Scholar
  2. 2.
    Arena JM, Drew RH: Poisoning. Toxicology. Symptoms. Treatments, 5th ed. Springfield, Charles C. Thomas, 1986.Google Scholar
  3. 3.
    Graef JW: Heavy metal poisoining, inHarrison’s Principles of Internal Medicine, Isselbacher KJ, Braunwald E, Wilson JD, Martin JB, Fauci AS, Kasper DL (eds.). New York, McGraw-Hill, 1994-1461.Google Scholar
  4. 4.
    Gritzka TL, Trump BF: Renal tubular lesions caused by mercuric chloride. Am J Pathol 1968; 52:1225–1250.PubMedGoogle Scholar
  5. 5.
    Bariety J, Druet P, Laliberte F, Sapin C: Glomerulonephritis with γ-and ΒlC-globulin deposits induced in rats by mercuric chloride. Am J Pathol 1971;65:293–302.PubMedGoogle Scholar
  6. 6.
    Sapin C, Druet E, Druet P: Induction of anti-glomerular basement membrane antibodies in the Brown-Norway rat by mercuric chloride. Clin Exp Immunol 1977; 28:173–179.PubMedGoogle Scholar
  7. 7.
    Mathieson PW: Mercuric chlorideinduced autoimmunity. Autoimmunity 1992;13:243–247.PubMedCrossRefGoogle Scholar
  8. 8.
    Goldman M, Druet P, Gleichmann E: TH2 cells in systemic autoimmunity: insights from allogeneic diseases and chemically-induced autoimmunity. Immunol Today 1991;12:223–227.PubMedCrossRefGoogle Scholar
  9. 9.
    Pusey CD, Bowman C, Morgan A, Weetman AP, Hartley B, Lockwood CM: Kinetics and pathogenicity of autoantibodies induced by mercuric chloride in the Brown Norway rat. Clin Exp Immunol 1990;81:76–82.PubMedCrossRefGoogle Scholar
  10. 10.
    Marriott JB, Qasim F, Oliveira DB: Anti-phospholipid antibodies in the mercuric chloride treated brown Norway rat. J Autoimmunity 1994;7:457–467.CrossRefGoogle Scholar
  11. 11.
    Robinson CJG, Balazs T, Egorov IK: Mercuric chloride-, gold sodium thiomalate-, and D-penicillamineinduced antinuclear antibodies in mice. Toxicol Appl Pharmacol 1986;86:159–169.PubMedCrossRefGoogle Scholar
  12. 12.
    Hultman P, Enestrom S, Pollard KM, Tan EM: Anti-fibrillarin antibodies in mercury-treated mice. Clin Exp Immunol 1989;78:470–477.PubMedGoogle Scholar
  13. 13.
    Reuter R, Tessars G, Vohr HW, Gleichmann E, Luhrmann R: Mercuric chloride induces autoantibodies against U3 small nuclear ribonucleoprotein in susceptible mice. Proc Natl Acad Sci USA 1989;86:237–241.PubMedCrossRefGoogle Scholar
  14. 14.
    Monestier M, Losman MJ, Novick KE, Aris JP: Molecular analysis of mercury-induced antinucleolar antibodies in H-2s mice. J Immunol 1994;152:667–675.PubMedGoogle Scholar
  15. 15.
    Hultman P, Turley SJ, Enestrom S, Lindh U, Pollard KM: Murine genotype influences the specificity, magnitude and persistence of murine mercury-induced autoimmunity. J Autoimmunity 1996;9: 139–146.CrossRefGoogle Scholar
  16. 16.
    Bowman C, Mason DW, Pusey CD, Lockwood CM: Autoregulation of autoantibody synthesis in mercuric chloride nephritis in the Brown Norway rat. I. A role for T suppressor cells. Eur J Immunol 1984;14:464–470.PubMedCrossRefGoogle Scholar
  17. 17.
    Mathieson PW, Stapleton KJ, Oliveira DB, Lockwood CM: Immunoregulation of mercuric chlorideinduced autoimmunity in Brown Norway rats: a role for CD8+ T cells revealed by in vivo depletion studies. Eur J Immunol 1991;21: 2105–2109.PubMedCrossRefGoogle Scholar
  18. 18.
    Castedo M, Pelletier L, Rossert J, Pasquier R, Villarroya H, Druet P: Mercury-induced autoreactive anticlass II T cell line protects from experimental autoimmune encephalomyelitis by the bias of CD8+ antiergotypic cells in Lewis rats. J Exp Med 1993;177:881–889.PubMedCrossRefGoogle Scholar
  19. 19.
    Pelletier L, Rossert J, Pasquier R, Vial MC, Druet P: Role of CD8+ T cells in mercury-induced autoimmunity or immunosuppression in the rat. Scand J Immunol 1990;31:65–74.PubMedCrossRefGoogle Scholar
  20. 20.
    Hanley GA, Schiffenbauer J, Sobel ES: Resistance to HgC12-induced autoimmunity in haplotypehet-erozygous mice is an intrinsic property of B cells. J Immunol 1998; 161:1778–1785.PubMedGoogle Scholar
  21. 21.
    Druet E, Sapin C, Gunther E, Feingold N, Druet P: Mercuric chloride-induced anti-glomerular basement membrane antibodies in the rat: genetic control. Eur J Immunol 1997;7:348–351.CrossRefGoogle Scholar
  22. 22.
    Sapin C, Mandet C, Druet E, Gunther E, Druet P: Immune complex type disease induced by HgC12 in Brown-Norway rats: genetic control of susceptibility. Clin Exp Immunol 1982;48:700–704.PubMedGoogle Scholar
  23. 23.
    Aten J, Veninga A, de Heer E, Rozing J, Nieuwenhuis P, Hoedemaeker PJ, et al:. Susceptibility to the induction of either autoimmunity or immunosuppression by mercuric chloride is related to the major histocompatibility complex class II haplotype. Eur J Immunol 1991;21:611–616.PubMedCrossRefGoogle Scholar
  24. 24.
    GoterRobinson CJ, White HJ, Rose NR: Murine strain differences in response to mercuric chloride: Antinucleolar antibodies production does not correlate with renal immune complex deposition. Clin Immunol Immunopathol 1997;83:127–138.CrossRefGoogle Scholar
  25. 25.
    GoterRobinson CJ, Abraham AA, Balazs T: Induction of anti-nuclear antibodies by mercuric chloride in mice. Clin Exp Immunol 1984;58: 300–306.Google Scholar
  26. 26.
    Mirtcheva J, Pfeiffer C, De Bruijn JA, Jacquesmart F, Gleichmann E: Immunological alterations induced by mercury compounds. III. H-2A acts as an immune response and H-2E as an immune response “suppression” locus for HgCl2-induced antinucleolar antibodies. Eur J Immunol 1989;19:2257–2261.PubMedCrossRefGoogle Scholar
  27. 27.
    Hultman P, Bell LJ, Enestrom S, Pollard KM: Murine susceptibility to mercury. I. Autoantibody profiles and systemic immune deposits in inbred, congenic, and intra-H-2 recombinant strains. Clin Immunol Immunopathol 1992;65:98–109.PubMedCrossRefGoogle Scholar
  28. 28.
    Hultman P, Bell LJ, Enestrom S, Pollard KM: Murine susceptibility to mercury. II. autoantibody profiles and renal immune deposits in hybrid, backcross, and H-2d congenic mice. Clin Immunol Immunopathol 1993;68:9–20.PubMedCrossRefGoogle Scholar
  29. 29.
    Hanley GA, Schiffenbauer J, Sobel ES: Class II haplotype differentially regulates immune response in HgCl2-treated mice. Clin Immunol Immunopathol 1997;84:328–337.PubMedCrossRefGoogle Scholar
  30. 30.
    Biancone L, Andres G, Ahn H, Lim A, Dai C, Noelle R, et al.: Distinct regulatory roles of lymphocyte costimulatory pathways on T helper type-2 mediated autoimmune disease. J Exp Med 1996; 183:1473–1481.PubMedCrossRefGoogle Scholar
  31. 31.
    Molina A, Sanchez-Madrid F. Bricio T, Martin A, Barat A, Alvarez V, et al.: Prevention of mercuric chloride-induced nephritis in the brown Norway rat by treatment with antibodies against the alpha 4 integrin. J Immunol 1994;153:2313–2320.PubMedGoogle Scholar
  32. 32.
    Hultman P, Johansson U, Turley SJ, Lindh U, Enestrom S, Pollard KM: Adverse immunological effects and autoimmunity induced by dental amalgam and alloy in mice. FASEB J1994;8:1183–1190.PubMedGoogle Scholar
  33. 33.
    Hultman P, Enestrom S. Turley SJ, Pollard KM: Selective induction of anti-fibrillarin autoantibodies by silver nitrate in mice. Clin Exp Immunol 1994;96:285–291.PubMedCrossRefGoogle Scholar
  34. 34.
    Schuhmann D, Kubicka-Muranyi M, Mirtschewa J, Gunther J, Kind P, Gleichmann E: Adverse immune reactions to gold. I. Chronic treatment with an Au(I) drug sensitizes mouse T cells not to Au(I), but to Au(III) and induces autoantibody formation. J Immunol 1990; 145: 2132–2139.PubMedGoogle Scholar
  35. 35.
    Ohsawa M, Takahashi K, Otsuka F: Induction of anti-nuclear antibodies in mice orally exposed to cadmium at low concentrations. Clin Exp Immunol 1988;73:98–102.PubMedGoogle Scholar
  36. 36.
    Monestier M, Novick KE, Losman MJ: D-penicillamine-and quinidine-induced antinuclear antibodies in A.SW (H-2s) mice: similarities with autoantibodies in spontaneous and heavy metal-induced autoimmunity. Eur J Immunol 1994;24: 723–730.PubMedCrossRefGoogle Scholar
  37. 37.
    Satoh M, Hamilton KJ, Ajmani AK, Dong X, Wang J, Kanwar YS, et al.: Autoantibodies to ribosomal P antigens with immune complex glomerulonephritis in SJL mice treated with pristane. J Immunol 1996;157:3200–3206.PubMedGoogle Scholar
  38. 38.
    Mosmann TR, Coffman RL: Differing patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989;7:145–173.PubMedCrossRefGoogle Scholar
  39. 39.
    Salgame P, Abrams JS, Clayberger C, Goldstein H, Convit J, Modlin RL, et al.: Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. Science 1991;254:279–282.PubMedCrossRefGoogle Scholar
  40. 40.
    Trinchieri G: Interleukin-12 and its role in the generation of TH1 cells. Immunol Today 1993; 14: 335–338.PubMedCrossRefGoogle Scholar
  41. 41.
    Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL: Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986;136:2348.PubMedGoogle Scholar
  42. 42.
    Hultman P, Johansson U, Dagnaes-Hansen F: Murine mercuryinduced autoimmunity: The role of T-helper cells. J Autoimmunity 1995;8:809–823.CrossRefGoogle Scholar
  43. 43.
    Prigent P, Saoudi A, Pannetier C, Graber P, Bonnefoy J-Y, Druet P, et al.: Mercuric chloride, a chemical responsible for T helper cell (Th)2-mediated autoimmunity in Brown Norway rats, directly triggers T cells to produce interleukin-4. J Clin Invest 1995;96: 1484–1489.PubMedGoogle Scholar
  44. 44.
    Oliveira DB, Gillespie K, Wolfreys K, Mathieson PW, Qasim F, Coleman JW: Compounds that induce autoimmunity in the Brown Norway rat sensitize mast cells for mediator release and interleukin-4 expression. Eur J Immunol 1995; 25:2259–2264.PubMedCrossRefGoogle Scholar
  45. 45.
    Van der Meide PH, de Labie MC, Botman CA, van Bennekom WP, Olsson T, Aten J, et al.: Mercuric chloride down-regulates T cell interferon-gamma production in brown Norway but not in Lewis rats; role of glutathione. Eur J Immunol 1993;23:675–681.PubMedCrossRefGoogle Scholar
  46. 46.
    Mathieson PW, Thiru S, Oliveira DB: Regulatory role of OX22high T cells in mercury-induced autoimmunity in the brown Norway rat. JExpMed1993;177:1309–1316.Google Scholar
  47. 47.
    van Vliet E, Uhrberg M, Stein C, Gleichmann E: MHC control of IL-4-dependent enhancement of B cell Ia expression and Ig class switching in mice treated with mercuric chloride. Int Arch Allergy Immunol 1993;101:392–401.PubMedGoogle Scholar
  48. 48.
    Bagenstose LM, Salgame P, Monestier M: IL-12 down-regulates autoantibody production in mercury-induced autoimmunity. J Immunol 1998;160:1612–1617.PubMedGoogle Scholar
  49. 49.
    Doth M, Fricke M, Nicoletti F, Garotta G, van Velthuysen ML, Bruijn JA, et al.: Genetic differences in immune reactivity to mercuric chloride (HgCl2): immunosuppression of H-2d mice is mediated by interferon-gamma (IFN-gamma). Clin Exp Immunol 1997;109:149–156.PubMedCrossRefGoogle Scholar
  50. 50.
    Ochel M, Vohr HW, Pfeiffer C, Gleichmann E: IL-4 is required for the IgE and IgG 1 increase and IgG 1 autoantibody formation in mice treated with mercuric chloride. J Immunol 1991;146:3006–3011.PubMedGoogle Scholar
  51. 51.
    Bagenstose LM, Salgame P, Monestier M: Mercury-induced autoimmunity in the absence of interleukin-4. Clin Exp Immunol 1998; 114:9–12.PubMedCrossRefGoogle Scholar
  52. 52.
    Kono DH, Balomenos D, Pearson DL, Park MS, Hildebrandt B, Hultman P, et al.: The prototypic Th2 autoimmunity induced by mercury is dependent on IFN-γ and not Th 1/ Th2 imbalance. J Immunol 1998; 161:234–240.PubMedGoogle Scholar
  53. 53.
    Hultman P, Ganowiak K, Turley SJ, Pollard KM: Genetic susceptibility to silver-induced antifibrillarin autoantibodies in mice. Clin Immunol Immunopathol 1995; 77:291–297.PubMedCrossRefGoogle Scholar
  54. 54.
    Johansson U, Hansson-Georgiadis H, Hultman P: Murine silver-induced autoimmunity: silver shares induction of antinucle-olar antibodies with mercury, but causes less activation of the immune system. Int Arch Allergy Immunol 1997;113: 432–443.PubMedGoogle Scholar
  55. 55.
    Jiang Y, Moller G: In vitro effects of HgC12 on murine lymphocytes. I. Preferable activation of CD4+ T cells in a responder strain. J Imm unol 1995;154. 3138–3146.Google Scholar
  56. 56.
    Hultman P, Enestrom S: The induction of immune complex deposits in mice by peroral and parenteral administration of mercuric chloride: strain dependent susceptibility. Clin Exp Immunol 1987;67: 283–292.PubMedGoogle Scholar
  57. 57.
    Stiller-Winkler R, Radaszkiewicz T, Gleichmann E: Immunopathological signs in mice treated with mercury compounds—I. Identification by the popliteal lymph node assay of responder and nonresponder strains. Int J Immunopharmacol 1988;10:475–484.PubMedCrossRefGoogle Scholar
  58. 58.
    Hu H, Abedi-Valugerdi M, Moller G: Pretreatment of lymphocytes with mercuryin vitro induces a response in T cells from genetically determined low-responders and a shift of the interleukin profile. Immunology 1997;90:198–204.PubMedCrossRefGoogle Scholar
  59. 59.
    Loftenius A, Ekstrand J, Möller E:In vitro effects of mercuric chloride (HgCl2) on human mononuclear cells. Clin Exp Immunol 1997;110:418–422.PubMedCrossRefGoogle Scholar
  60. 60.
    Pelletier L, Pasquier R, Guettier C, Vial MC, Mandet C, Nochy D, et al.: HgC 12 induces T and B cells to proliferate and differentiate in BN rats. Clin Exp Immunol 1988; 71:336–342.PubMedGoogle Scholar
  61. 61.
    Hirsch F, Couderc J, Sapin C, Fournie G, Druet P: Polyclonal effect of HgCl2 in the rat, its possible role in an experimental autoimmune disease. Eur J Immunol 1982;12:620–625.PubMedCrossRefGoogle Scholar
  62. 62.
    Hu H, Moller G, Abedi-Valugerdi M: Major histocompatibility complex class II antigens are required for both cytokine production and proliferation induced by mercuric chloride in vitro. J Autoimmunity 1997;10:441–446.CrossRefGoogle Scholar
  63. 63.
    Johansson U, Sander B, Hultman P: Effects of the murine genotype on T cell activation and cytokine production in murine mercury-induced autoimmunity. J Autoimmunity 1997;10:347–355.CrossRefGoogle Scholar
  64. 64.
    Badou A, Savignac M, Moreau M, Leclerc C, Pasquier R, Druet P, etal.: HgCl2-induced interleukin-4 gene expression in T cells involves a protein kinase C-dependent calcium influx through L-type calcium channels. J Biol Chem 1997; 272:32,411–32,418.CrossRefGoogle Scholar
  65. 65.
    Meister A, Anderson ME: Glutathione. Annu Rev Biochem 1983; 52:711–760.PubMedCrossRefGoogle Scholar
  66. 66.
    Jeannin P, Delneste Y, Lecoanet-Henchoz S, Gauchat JF, Life P, Holmes D, et al.: Thiols decrease human interleukin (IL) 4 production and IL-4-induced immunoglobulin synthesis. J Exp Med 1995;182:1785–1792.PubMedCrossRefGoogle Scholar
  67. 67.
    Peterson JD, Herzenberg LA, Vasquez K, Waltenbaugh C: Glutathione levels in antigen-presenting cells modulate Thl versus Th2 response patterns. Proc Natl Acad SciUSA1998;95:3071–3076.CrossRefGoogle Scholar
  68. 68.
    Hu H, Moller G, Abedi-Valugerdi M: Thiol compounds inhibit mercury-induced immunological and immunopathological alterations in susceptible mice. Clin Exp Immunol 1997; 107:68–75.PubMedCrossRefGoogle Scholar
  69. 69.
    Ochs RL: Methods used to study structure and function of the nucleolus. Methods Cell Biol 1998;53: 303–321.PubMedGoogle Scholar
  70. 70.
    Rosen A, Casciola-Rosen L: Environmental determinants of autoimmune disease, inThe Autoimmune Diseases. Rose NR, Mackay IR (eds.). San Diego, Academic, 1998, p. 119.Google Scholar
  71. 71.
    Griem P, Gleichmann E: Metal ion induced autoimmunity. Current Opinion Immunol 1995;7: 831–838.CrossRefGoogle Scholar
  72. 72.
    Griem P, Panthel K, Kaibacher H, Gleichmann E: Alteration of a model antigen by Au(III) leads to T cell sensitization to cryptic peptides. Eur J Immunol 1996;26: 279–287.PubMedCrossRefGoogle Scholar
  73. 73.
    Kubicka-Muranyi M, Griem P, Lubben B, Rottmann N, Luhrmann R, Gleichmann E: Mercuric-chloride-induced autoimmunity in mice involves up-regulated presentation by spleen cells of altered and unaltered nucleolar self antigen. Int Arch Allergy Immunol 1995; 108:1–10.PubMedGoogle Scholar
  74. 74.
    Kubicka-Muranyi M, Kremer J, Rottmann N, Lubben B, Albers R, Bloksma N, Luhrmann R, Gleichmann E: Murine systemic autoimmune disease induced by mercuric chloride: T helper cells reacting to self-proteins. Int Arch Allergy Immunol 1996;109:ll-20.CrossRefGoogle Scholar
  75. 75.
    Goyer RA: Environmentally related diseases of the urinary tract. Med Clin North Am 1990; 74:377–389.PubMedGoogle Scholar
  76. 76.
    Enestrom S, Hultman P: Does amalgam affect the immune system? A controversial issue. Int Arch Allergy Immunol 1995;106: 180–203.PubMedCrossRefGoogle Scholar
  77. 77.
    Röger J, Zillikens D, Hartmann AA, Burg G, Gleichmann E: Systemic autoimmune disease in a patient with long-standing exposure to mercury. Eur J Dermatol 1992;2:168–170, 1992.Google Scholar
  78. 78.
    Moszczynski P, Slowinski S, Rutkowski J, Bern S, Jakus-Stoga D: Lymphocytes, T and NK cells, in men occupationally exposed to mercury vapours. Int J Occupational Med Environ Health 1995;8:49–56.Google Scholar
  79. 79.
    Cardenas A, Roels H, Bernard AM, Barbon R, Buchet JP, Rosello J, et al.: Markers of early renal changes induced by industrial pollutants. I. Application to workers exposed to mercury vapors. Br J IndMed1998;50:17–27.Google Scholar
  80. 80.
    Dantas DC, Queiroz ML: Immunoglobulin E and autoantibodies in mercury-exposed workers. Immunopharmacol Immunotoxicol 1997;19:383–392.PubMedGoogle Scholar
  81. 81.
    Warfvinge K, Hansson H, Hultman P: Systemic autoimmunity due to mercury vapor exposure in genetically susceptible mice: doseresponse studies. Toxicol Appl Pharmacol 1995; 132:299–309.PubMedCrossRefGoogle Scholar
  82. 82.
    Lorscheider FL, Vimy MJ, Summers AO: Mercury exposure from “silver” tooth fillings: emerging evidence questions a traditional dental paradigm. FASEB J 1995; 9:504–508.PubMedGoogle Scholar
  83. 83.
    Kilburn KH, Warshaw RH: Prevalence of symptoms of systemic lupus erythematosus (SLE) and of fluorescent antinuclear antibodies associated with chronic exposure to trichloroethylene and other chemicals in well water. Environ Res 1992;57:l-9.CrossRefGoogle Scholar
  84. 84.
    Monestier M, Kotzin BL: Antibodies to histones in systemic lupus erythematosus and druginduced lupus syndromes. Rheum Dis Clin North Am 1992;18: 415–436.PubMedGoogle Scholar
  85. 85.
    Rothfield NF: Autoantibodies in scleroderma. Rheum Dis Clin North Am 1992;18:483–498.PubMedGoogle Scholar
  86. 86.
    Silman AJ: Epidemiology of scleroderma. Ann Rheum Dis 1991; 50:846–853.PubMedGoogle Scholar
  87. 87.
    Monestier M: Nucleolar autoantibodies, inAutoantibodies. Peter JB, Shoenfeld Y (eds.). Amsterdam, Elsevier, 1996, p. 567.Google Scholar
  88. 88.
    Takeuchi K, Turley SJ, Tan EM, Pollard KM: Analysis of the autoantibody response to fibrillarin in human disease and murine models of autoimmunity. J Immunol 1995 ;154:961–971.PubMedGoogle Scholar
  89. 89.
    Arnett FC, Reveille JD, Goldstein R, Pollard KM, Leaird K, Smith EA, et al.: Autoantibodies to fibrillarin in systemic sclerosis (scleroderma). An immunogenetic, serologic, and clinical analysis. Arthritis Rheum 1996;39:1151–1160.PubMedCrossRefGoogle Scholar
  90. 90.
    Mavilia C, Scaletti C, Romagnani P, Carossino A, Pignone A, Emmi, et al.: Type 2 helper T-cell predominance and high CD30 expression in systemic sclerosis. Am J Pathol 1997;151:1571–1578.Google Scholar
  91. 91.
    Bigazzi P: Autoimmunity induced by chemicals. Clin Toxicol 1988; 26:125–156.CrossRefGoogle Scholar
  92. 92.
    Gleichmann E, Kimber I, Purchase IFH: Immunotoxicology: suppressive and stimulatory effects of drugs and environmental chemicals on the immune system. Arch Toxicol 1989 ; 63: 257–273.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 1999

Authors and Affiliations

  • Lee M. Bagenstose
    • 1
  • Padmini Salgame
    • 1
  • Marc Monestier
    • 1
  1. 1.Department of Microbiology and ImmunologyTemple University School of MedicinePhiladelphia

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