Toxin-induced immunological renal disease

  • Lucette Pelletier
  • Abdelhadi Saoudi
  • Gilbert Fournié

The last years have provided insight as to how lymphocytes respond to antigen or xenobiotics, and have increased our understanding of the pathophysiology of renal diseases. This points out new clues on the mechanisms by which chemically-induced immune response trigger immune nephropathies. We will describe the T-cell subsets including Th1 and Th2 cells that may be implicated in renal inflammation. The role of Th1 and Th2 CD4+ T-cell subsets in the development of some nephropathies will be debated. Then, we will evoke the mechanism by which a drug or its metabolites may trigger autoimmunity or hypersensitivity reactions. Third, we will report nephropathies induced by xenobiotics in patients, emphasizing the possible underlying mechanisms. Fourth, we will focus on some experimental models of chemical-induced systemic autoimmune diseases that illustrate mechanisms described before. Finally, we will discuss recent insights from these models onto the genetic control of susceptibility to drug-induced immunopathology. This will allow us to introduce the impact of genetic studies in our understanding of the pathogenesis of immune nephropathies, which undoubtedly in the future will shed new light on toxin-induced nephropathies.


Idiopathic Nephrotic Syndrome Minimal Change Nephrotic Syndrome Crescentic Glomerulonephritis Gold Salt Tubulointerstitial Nephritis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Rengarajan J, Szabo SJ, Glimcher LH: Transcriptional regulation of Th1/Th2 polarization. Immunol. Today 2000; 21: 479-83.PubMedGoogle Scholar
  2. 2.
    Tipping PG, Kitching AR: Glomerulonephritis, Th1 and Th2: what’s new? Clin Exp Immunol 2005; 142: 207-15.PubMedGoogle Scholar
  3. 3.
    Romagnani S: Regulation of the T cell response. Clin Exp Allergy 2006; 36: 1357-66.PubMedGoogle Scholar
  4. 4.
    Harrington LE, Mangan PR, Weaver CT: Expanding the effector CD4 T-cell repertoire: the Th17 lineage. Curr Opin Immunol 2006; 18: 349-56.PubMedGoogle Scholar
  5. 5.
    MacKay CR: Follicular homing T helper (Th) cells and the Th1/Th2 paradigm. J. Exp. Med. 2000; 192: F31-F34.PubMedGoogle Scholar
  6. 6.
    Glimcher LH, Murphy KM: Lineage commitment in the immune system: the T helper lymphocyte grows up. Genes Dev. 2000; 14: 1693-711.PubMedGoogle Scholar
  7. 7.
    Ivanov, II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR: The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 2006; 126: 1121-33.PubMedGoogle Scholar
  8. 8.
    Lohr J, Knoechel B, Abbas AK: Regulatory T cells in the periphery. Immunol Rev 2006; 212: 149-62.PubMedGoogle Scholar
  9. 9.
    Guéry JC, Galbiati F, Smiroldo S, Adorini L: Selective development of T helper (Th)2 cells induced by continuous administration of low dose soluble proteins to normal and b2-microglobulin-deficient BALB/c mice. J. Exp. Med. 1996; 183: 485-497.PubMedGoogle Scholar
  10. 10.
    Foucras G, Gallard A, Coureau C, Kanellopoulos JM, Guery JC: Chronic soluble antigen sensitization primes a unique memory/effector T cell repertoire associated with th2 phenotype acquisition in vivo. J Immunol 2002; 168: 179-87.PubMedGoogle Scholar
  11. 11.
    Feili-Hariri M, Falkner DH, Morel PA: Polarization of naive T cells into Th1 or Th2 by distinct cytokine-driven murine dendritic cell populations: implications for immunotherapy. J Leukoc Biol 2005; 78: 656-64.PubMedGoogle Scholar
  12. 12.
    Liu YJ, Soumelis V, Watanabe N, Ito T, Wang YH, Malefyt RD, Omori M, Zhou B, Ziegler SF: TSLP: An Epithelial Cell Cytokine thaTregulates T Cell Differentiation by Conditioning Dendritic Cell Maturation. Annu Rev Immunol 2006;Google Scholar
  13. 13.
    Gomes B, Savignac M, Moreau M, Leclerc C, Lory P, Guery JC, Pelletier L: Lymphocyte calcium signaling involves dihydropyridine-sensitive L-type calcium channels: facts and controversies. Crit Rev Immunol 2004; 24: 425-48.PubMedGoogle Scholar
  14. 14.
    Grogan JL, Mohrs M, Harmon B, Lacy DA, Sedat JW, Locksley RM: Early transcription and silencing of cytokine genes underlie polarization of T helper cell subsets. Immunity 2001; 14: 205-15.PubMedGoogle Scholar
  15. 15.
    Spilianakis CG, Lalioti MD, Town T, Lee GR, Flavell RA: Interchromosomal associations between alternatively expressed loci. Nature 2005; 435: 637-45.PubMedGoogle Scholar
  16. 16.
    Lee GR, Kim ST, Spilianakis CG, Fields PE, Flavell RA: T helper cell differentiation: regulation by cis elements and epigenetics. Immunity 2006; 24: 369-79.PubMedGoogle Scholar
  17. 17.
    Tipping PG, Timoshanko J: Contributions of intrinsic renal cells to crescentic glomerulonephritis. Nephron Exp Nephrol 2005; 101: e173-8.Google Scholar
  18. 18.
    Holdsworth SR, Kitching AR, Tipping PG: Th1 and Th2 T helper cell subsets affect patterns of injury and outcomes in glomerulonephritis. Kidney Int 1999; 55: 1198-216.PubMedGoogle Scholar
  19. 19.
    Le Berre L, Herve C, Buzelin F, Usal C, Soulillou JP, Dantal J: Renal macrophage activation and Th2 polarization precedes the development of nephrotic syndrome in Buffalo/Mna rats. Kidney Int 2005; 68: 2079-90.PubMedGoogle Scholar
  20. 20.
    van den Berg JG, Weening JJ: Role of the immune system in the pathogenesis of idiopathic nephrotic syndrome. Clin Sci (Lond) 2004; 107: 125-36.Google Scholar
  21. 21.
    Wei CL, Cheung W, Heng CK, Arty N, Chong SS, Lee BW, Puah KL, Yap HK: Interleukin-13 genetic polymorphisms in Singapore Chinese children correlate with long-term outcome of minimal-change disease. Nephrol Dial Transplant 2005; 20: 728-34.PubMedGoogle Scholar
  22. 22.
    Acharya B, Shirakawa T, Pungky A, Damanik P, Massi MN, Miyata M, Matsuo M, Gotoh A: Polymorphism of the interleukin-4, interleukin-13, and signal transducer and activator of transcription 6 genes in Indonesian children with minimal change nephrotic syndrome. Am J Nephrol 2005; 25: 30-5.PubMedGoogle Scholar
  23. 23.
    Ruotsalainen V, Ljungberg P, Wartiovaara J, Lenkkeri U, Kestila M, Jalanko H, Holmberg C, Tryggvason K: Nephrin is specifically located at the slit diaphragm of glomerular podocytes. Proc Natl Acad Sci U S A 1999; 96: 7962-7.PubMedGoogle Scholar
  24. 24.
    Shih NY, Li J, Karpitskii V, Nguyen A, Dustin ML, Kanagawa O, Miner JH, Shaw AS: Congenital nephrotic syndrome in mice lacking CD2-associated protein. Science 1999; 286: 312-5.PubMedGoogle Scholar
  25. 25.
    Togawa A, Miyoshi J, Ishizaki H, Tanaka M, Takakura A, Nishioka H, Yoshida H, Doi T, Mizoguchi A, Matsuura N, Niho Y, Nishimune Y, Nishikawa Si, Takai Y: Progressive impairment of kidneys and reproductive organs in mice lacking Rho GDIalpha. Oncogene 1999; 18: 5373-80.PubMedGoogle Scholar
  26. 26.
    Kaplan JM, Kim SH, North KN, Rennke H, Correia LA, Tong HQ, Mathis BJ, Rodriguez-Perez JC, Allen PG, Beggs AH, Pollak MR: Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. Nat Genet 2000; 24: 251-6.PubMedGoogle Scholar
  27. 27.
    Pavenstadt H: Roles of the podocyte in glomerular function. Am J Physiol Renal Physiol 2000; 278: F173-9.PubMedGoogle Scholar
  28. 28.
    Johnson RJ: New insights into the pathogenesis of proteinuria. Am J Kidney Dis 2000; 36: 214-9.PubMedGoogle Scholar
  29. 29.
    Putaala H, Soininen R, Kilpelainen P, Wartiovaara J, Tryggvason K: The murine nephrin gene is specifically expressed in kidney, brain and pancreas: inactivation of the gene leads to massive proteinuria and neonatal death. Hum. Mol. Genet. 2001; 10: 1-8.PubMedGoogle Scholar
  30. 30.
    Koukouritaki SB, Vardaki EA, Papakonstanti EA, Lianos E, Stournaras C, Emmanouel DS: TNF-alpha induces actin cytoskeleton reorganization in glomerular epithelial cells involving tyrosine phosphorylation of paxillin and focal adhesion kinase. Mol Med 1999; 5: 382-92.PubMedGoogle Scholar
  31. 31.
    Doublier S, Ruotsalainen V, Salvidio G, Lupia E, Biancone L, Conaldi PG, Reponen P, Tryggvason K, Camussi G: Nephrin redistribution on podocytes is a potential mechanism for proteinuria in patients with primary acquired nephrotic syndrome. Am J Pathol 2001; 158: 1723-31.PubMedGoogle Scholar
  32. 32.
    Nangaku M, Shankland SJ, Couser WG: Cellular response to injury in membranous nephropathy. J Am Soc Nephrol 2005; 16: 1195-204.PubMedGoogle Scholar
  33. 33.
    Van Den Berg JG, Aten J, Chand MA, Claessen N, Dijkink L, Wijdenes J, Lakkis FG, Weening JJ: Interleukin-4 and interleukin-13 act on glomerular visceral epithelial cells. J Am Soc Nephrol 2000; 11: 413-22.PubMedGoogle Scholar
  34. 34.
    Wolf D, Hochegger K, Wolf AM, Rumpold HF, Gastl G, Tilg H, Mayer G, Gunsilius E, Rosenkranz AR: CD4+CD25+ regulatory T cells inhibit experimental anti-glomerular basement membrane glomerulonephritis in mice. J Am Soc Nephrol 2005; 16: 1360-70.PubMedGoogle Scholar
  35. 35.
    Mahajan D, Wang Y, Qin X, Zheng G, Wang YM, Alexander SI, Harris DC: CD4+CD25+ regulatory T cells protect against injury in an innate murine model of chronic kidney disease. J Am Soc Nephrol 2006; 17: 2731-41.PubMedGoogle Scholar
  36. 36.
    Wang YM, Zhang GY, Wang Y, Hu M, Wu H, Watson D, Hori S, Alexander IE, Harris DC, Alexander SI: Foxp3-transduced polyclonal regulatory T cells protect against chronic renal injury from adriamycin. J Am Soc Nephrol 2006; 17: 697-706.PubMedGoogle Scholar
  37. 37.
    Gallucci S, Matzinger P: Danger signals: SOS to the immune system. Curr Opin Immunol 2001; 13: 114-9.PubMedGoogle Scholar
  38. 38.
    Blander JM, Medzhitov R: Toll-dependent selection of microbial antigens for presentation by dendritic cells. Nature 2006; 440: 808-12.PubMedGoogle Scholar
  39. 39.
    Inaba K, Turley S, Iyoda T, Yamaide F, Shimoyama S, Reis e Sousa C, Germain RN, Mellman I, Steinman RM: The formation of immunogenic major histocompatibility complex class II- peptide ligands in lysosomal compartments of dendritic cells is regulated by inflammatory stimuli. J Exp Med 2000; 191: 927-36.PubMedGoogle Scholar
  40. 40.
    Aeby P, Wyss C, Beck H, Griem P, Scheffler H, Goebel C: Characterization of the sensitizing potential of chemicals by in vitro analysis of dendritic cell activation and skin penetration. J Invest Dermatol 2004; 122: 1154-64.PubMedGoogle Scholar
  41. 41.
    Uetrecht J: Role of animal models in the study of drug-induced hypersensitivity reactions. Aaps J 2005; 7: E914-21.Google Scholar
  42. 42.
    Manome H, Aiba S, Tagami H: Simple chemicals can induce maturation and apoptosis of dendritic cells. Immunology 1999; 98: 481-90.PubMedGoogle Scholar
  43. 43.
    Rodriguez-Pena R, Lopez S, Mayorga C, Antunez C, Fernandez TD, Torres MJ, Blanca M: Potential involvement of dendritic cells in delayed-type hypersensitivity reactions to beta-lactams. J Allergy Clin Immunol 2006; 118: 949-56.PubMedGoogle Scholar
  44. 44.
    Olsen NJ: Drug-induced autoimmunity. Best Pract Res Clin Rheumatol 2004; 18: 677-88.PubMedGoogle Scholar
  45. 45.
    Pollard KM, Lee DK, Casiano CA, Bluthner M, Johnston MM, Tan EM: The autoimmunity-inducing xenobiotic mercury interacts with the autoantigen fibrillarin and modifies its molecular and antigenic properties. J Immunol 1997; 158: 3521-8.PubMedGoogle Scholar
  46. 46.
    Kubicka-Muranyi M, Behmer O, Uhrberg M, Klonowski H, Bister J, Gleichmann E: Murine systemic autoimmune disease induced by mercuric chloride (HgCl2) : Hg-specific helper T-cells react to antigen stored in macrophages. Int. J. Immunopharmac. 1993; 15: 151-61.Google Scholar
  47. 47.
    Mamula MJ, Lin R-H, Janeway Jr CA: Breaking T cell tolerance with foreign and self co-immunogens A study of autoimmune B and T cell epitopes of cytochrome c. J. Immunol. 1992; 149: 789-95.PubMedGoogle Scholar
  48. 48.
    Gamerdinger K, Moulon C, Karp DR, Van Bergen J, Koning F, Wild D, Pflugfelder U, Weltzien HU: A new type of metal recognition by human T cells: contact residues for peptide-independent bridging of T cell receptor and major histocompatibility complex by nickel. J Exp Med 2003; 197: 1345-53.PubMedGoogle Scholar
  49. 49.
    Moulon C, Choleva Y, Thierse HJ, Wild D, Weltzien HU: T cell receptor transfection shows non-HLA-restricted recognition of nickel by CD8+ human T cells to be mediated by alphabeta T cell receptors. J Invest Dermatol 2003; 121: 496-501.PubMedGoogle Scholar
  50. 50.
    Pichler WJ, Beeler A, Keller M, Lerch M, Posadas S, Schmid D, Spanou Z, Zawodniak A, Gerber B: Pharmacological interaction of drugs with immune receptors: the p-i concept. Allergol Int 2006; 55: 17-25.PubMedGoogle Scholar
  51. 51.
    Beeler A, Engler O, Gerber BO, Pichler WJ: Long-lasting reactivity and high frequency of drug-specific T cells after severe systemic drug hypersensitivity reactions. J Allergy Clin Immunol 2006; 117: 455-62.PubMedGoogle Scholar
  52. 52.
    Schmid DA, Depta JP, Luthi M, Pichler WJ: Transfection of drug-specific T-cell receptors into hybridoma cells: tools to monitor drug interaction with T-cell receptors and evaluate cross-reactivity to related compounds. Mol Pharmacol 2006; 70: 356-65.PubMedGoogle Scholar
  53. 53.
    Dustin ML, Cooper JA: The immunological synapse and the actin cytoskeleton: molecular hardware for T cell signaling. Nat Immunol 2000; 1: 23-9.PubMedGoogle Scholar
  54. 54.
    Cemerski S, Shaw A: Immune synapses in T-cell activation. Curr Opin Immunol 2006; 18: 298-304.PubMedGoogle Scholar
  55. 55.
    Revy P, Sospedra M, Barbour B, Trautmann A: Functional antigen-independent synapses formed between T cells and dendritic cells. Nat Immunol 2001; 2: 925-31.PubMedGoogle Scholar
  56. 56.
    Billadeau DD, Nolz JC, Gomez TS: Regulation of T-cell activation by the cytoskeleton. Nat Rev Immunol 2007; 7: 131-43.PubMedGoogle Scholar
  57. 57.
    Pu MY, Akhand AA, Kato M, Koike T, Hamaguchi M, Suzuki H, Nakashima I: Mercuric chloride mediates a protein sulfhydrylmodification-based pathway of signal transduction for activating Src kinase which is independent of the phosphorylation/de- phosphorylation of a carboxyl terminal tyrosine. J Cell Biochem 1996; 63: 104-14.PubMedGoogle Scholar
  58. 58.
    Savignac M, Badou A, Delmas C, Subra JF, De Cramer S, Paulet P, Cassar G, Druet P, Saoudi A, Pelletier L: Gold is a T cell polyclonal activator in BN and LEW rats but favors IL-4 expression only in autoimmune prone BN rats. Eur. J. Immunol. 2001; 31: 2266-2276.PubMedGoogle Scholar
  59. 59.
    Griem P, Gleichmann E: Metal ion-induced autoimmunity. Curr. Opin. Immunol. 1995; 7: 831-838.PubMedGoogle Scholar
  60. 60.
    Griem P, von Vultee C, Panthel K, Best SL, Sadler PJ, Shaw CF, 3rd: T cell cross-reactivity to heavy metals: identical cryptic peptides may be presented from protein exposed to different metals. Eur J Immunol 1998; 28: 1941-7.PubMedGoogle Scholar
  61. 61.
    Wulferink M, Dierkes S, Gleichmann E: Cross-sensitization to haptens: formation of common haptenic metabolites, T cell recognition of cryptic peptides, and true T cell cross-reactivity. Eur J Immunol 2002; 32: 1338-48.PubMedGoogle Scholar
  62. 62.
    Weiss RA, Madaio MP, Tomaszewski JE, Kelly CJ: T cells reactive to an inducible heat shock protein induce disease in toxin-induced interstitial nephritis. J. Exp. Med. 1994; 180: 2239-2250.PubMedGoogle Scholar
  63. 63.
    Pillinger MH, Staud R: Propylthiouracil and antineutrophil cytoplasmic antibody associated vasculitis: the detective finds a clue. Semin Arthritis Rheum 2006; 36: 1-3.PubMedGoogle Scholar
  64. 64.
    Gao Y, Chen M, Ye H, Guo XH, Zhao MH, Wang HY: The target antigens of antineutrophil cytoplasmic antibodies (ANCA) induced by propylthiouracil. Int Immunopharmacol 2007; 7: 55-60.PubMedGoogle Scholar
  65. 65.
    Bonaci-Nikolic B, Nikolic MM, Andrejevic S, Zoric S, Bukilica M: Antineutrophil cytoplasmic antibody (ANCA)-associated autoimmune diseases induced by antithyroid drugs: comparison with idiopathic ANCA vasculitides. Arthritis Res Ther 2005; 7: R1072-81.PubMedGoogle Scholar
  66. 66.
    Griem P, Panthel K, Kalbacher 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.PubMedGoogle Scholar
  67. 67.
    Kalluri R, Cantley LG, Kerjaschki D, Neilson EG: Reactive oxygen species expose cryptic epitopes associated with autoimmune goodpasture syndrome. J Biol Chem 2000; 275: 20027-32.PubMedGoogle Scholar
  68. 68.
    Stockinger B: T lymphocyte tolerance: from thymic deletion to peripheral control mechanisms. Adv. Immunol. 1999; 71: 229-65.PubMedGoogle Scholar
  69. 69.
    Klein L, Kyewski B„Promiscuous“ expression of tissue antigens in the thymus: a key to T- cell tolerance and autoimmunity? J Mol Med 2000; 78: 483-94.PubMedGoogle Scholar
  70. 70.
    Buer J, Lanoue A, Franzke A, Garcia C, von Boehmer H, Sarukhan A: Interleukin 10 secretion and impaired effector function of major histocompatibility complex class II-restricted T cells anergized in vivo. J Exp Med 1998; 187: 177-83.PubMedGoogle Scholar
  71. 71.
    Hess AD, Thoburn CJ: Immune tolerance to self-major histocompatibility complex class II antigens after bone marrow transplantation: role of regulatory T cells. Biol Blood Marrow Transplant 2006; 12: 518-29.PubMedGoogle Scholar
  72. 72.
    Choudhury D, Ahmed Z: Drug-associated renal dysfunction and injury. Nat Clin Pract Nephrol 2006; 2: 80-91.PubMedGoogle Scholar
  73. 73.
    Markowitz GS, Perazella MA: Drug-induced renal failure: a focus on tubulointerstitial disease. Clin Chim Acta 2005; 351: 31-47.PubMedGoogle Scholar
  74. 74.
    Spanou Z, Keller M, Britschgi M, Yawalkar N, Fehr T, Neuweiler J, Gugger M, Mohaupt M, Pichler WJ: Involvement of drug-specific T cells in acute drug-induced interstitial nephritis. J Am Soc Nephrol 2006; 17: 2919-27.PubMedGoogle Scholar
  75. 75.
    Burgess JK, Lopez JA, Gaudry LE, Chong BH: Rifampicin-dependent antibodies bind a similar or identical epitope to glycoprotein IX-specific quinine-dependent antibodies. Blood 2000; 95: 1988-92.PubMedGoogle Scholar
  76. 76.
    De Vriese AS, Robbrecht DL, Vanholder RC, Vogelaers DP, Lameire NH: Rifampicin-associated acute renal failure: pathophysiologic, immunologic, and clinical features. Am J Kidney Dis 1998; 31: 108-15.PubMedGoogle Scholar
  77. 77.
    Ravnskov U: Glomerular, tubular and interstitial nephritis associated with non- steroidal anti-inflammatory drugs. Evidence of a common mechanism. Br J Clin Pharmacol 1999; 47: 203-10.PubMedGoogle Scholar
  78. 78.
    Markowitz GS, Radhakrishnan J, Kambham N, Valeri AM, Hines WH, D‘Agati VD: Lithium nephrotoxicity: a progressive combined glomerular and tubulointerstitial nephropathy. J Am Soc Nephrol 2000; 11: 1439-48.PubMedGoogle Scholar
  79. 79.
    Shah P, Griffith SM, Shadforth MF, Fisher J, Dawes PT, Poulton KV, Thomson W, Ollier WE, Mattey DL: Can gold therapy be used more safely in rheumatoid arthritis? Adverse drug reactions are more likely in patients with nodular disease, independent of HLA-DR3 status. J Rheumatol 2004; 31: 1903-5.PubMedGoogle Scholar
  80. 80.
    Habib GS, Saliba W, Nashashibi M, Armali Z: Penicillamine and nephrotic syndrome. Eur J Intern Med 2006; 17: 343-8.PubMedGoogle Scholar
  81. 81.
    Pirmohamed M: Genetic factors in the predisposition to drug-induced hypersensitivity reactions. Aaps J 2006; 8: E20-6.PubMedGoogle Scholar
  82. 82.
    Wooley PH, Griffin J, Panayi GS, Batchelor JR, Welsh KI, Gibson TJ: HLA-DR antigens and toxic reaction to sodium aurothiomalate and D-penicillamine in patients with rheumatoid arthritis. N. Engl. J. Med. 1980; 303: 300-302.PubMedCrossRefGoogle Scholar
  83. 83.
    Emery P, Panayi GS, Huston G, Welsh KL, Mitschell SC, Shah RR, Idle JR, Smith RL, Waring RH: D-penicillamine induced toxicity in rheumatoid arthritis : the role of sulphoxidation status and HLA-DR3. J. Rheum. 1984; 11: 626-632.PubMedGoogle Scholar
  84. 84.
    Pospishil YO, Antonovych TM: NSAIDs associated nephropathy. Pol J Pathol 1998; 49: 35-9.PubMedGoogle Scholar
  85. 85.
    Makino H, Haramoto T, Sasaki T, Hironaka K, Shikata K, Takahashi K, Ota Z: Massive eosinophilic infiltration in a patient with the nephrotic syndrome and drug-induced interstitial nephritis. Am J Kidney Dis 1995; 26: 62-7.PubMedGoogle Scholar
  86. 86.
    Dharnidharka VR, Rosen S, Somers MJ: Acute interstitial nephritis presenting as presumed minimal change nephrotic syndrome. Pediatr Nephrol 1998; 12: 576-8.PubMedGoogle Scholar
  87. 87.
    Yawalkar N, Hari Y, Frutig K, Egli F, Wendland T, Braathen LR, Pichler WJ: T cells isolated from positive epicutaneous test reactions to amoxicillin and ceftriaxone are drug specific and cytotoxic. J Invest Dermatol 2000; 115: 647-52.PubMedGoogle Scholar
  88. 88.
    Brugnolo F, Annunziato F, Sampognaro S, Campi P, Manfredi M, Matucci A, Blanca M, Romagnani S, Maggi E, Parronchi P: Highly Th2-skewed cytokine profile of beta-lactam-specific T cells from nonatopic subjects with adverse drug reactions. J Immunol 1999; 163: 1053-9.PubMedGoogle Scholar
  89. 89.
    Padovan E, von Greyerz S, Pichler WJ, Weltzien HU: Antigen-dependent and -independent IFN-gamma modulation by penicillins. J Immunol 1999; 162: 1171-7.PubMedGoogle Scholar
  90. 90.
    Deckers JG, De Haij S, van der Woude FJ, van der Kooij SW, Daha MR, van Kooten C: IL-4 and IL-13 augment cytokine- and CD40-induced RANTES production by human renal tubular epithelial cells in vitro. J Am Soc Nephrol 1998; 9: 1187-93.PubMedGoogle Scholar
  91. 91.
    Cornacchia E, Golbus J, Maybaum J, Strahler J, Hanash S, Richardson B: Hydralazine and procainamide inhibit T cell DNA methyla-tion and induce autoreactivity. J. Immunol. 1988; 140: 2197-2200.PubMedGoogle Scholar
  92. 92.
    Quddus J, Johnson K, Gavalchin J, Amento E, Chrisp C, Yung R, Richardson B: Treating activated CD4+ T cells with either of two distinct methyltransferase inhibitors, 5-azacytidine or procainamide, is sufficient to cause a lupus-like disease in syngeneic mice. J. Clin. Invest. 1993; 92: 38-46.PubMedGoogle Scholar
  93. 93.
    Kretz-Rommel A, Duncan SR, Rubin RL: Autoimmunity caused by disruption of central T cell tolerance. A murine model of druginduced lupus. J Clin Invest 1997; 99: 1888-96.PubMedGoogle Scholar
  94. 94.
    Rubin RL: Drug-induced lupus. Toxicology 2005; 209: 135-47.PubMedGoogle Scholar
  95. 95.
    Uetrecht J: Current trends in drug-induced autoimmunity. Autoimmun Rev 2005; 4: 309-14.PubMedGoogle Scholar
  96. 96.
    Richardson B, Powers D, Hooper F, Yung RL, O’Rourke K: Lymphocyte function-associated antigen 1 overexpression and T cell autoreactivity. Arthritis Rheum 1994; 37: 1363-72.PubMedGoogle Scholar
  97. 97.
    Yung RL, Quddus J, Chrisp CE, Johnson KJ, Richardson BC: Mechanisms of drug-induced lupus I. Clones Th2 cells modified with DNA methylation inhibitors in vitro cause autoimmunity in vivo. J. Immunol. 1995; 154: 3025-3035.PubMedGoogle Scholar
  98. 98.
    Yung R, Powers D, Johnson K, Amento E, Carr D, Laing T, Yang J, Chang S, Hemati N, Richardson B: Mechanisms of drug-induced lupus. II. T cells overexpressing lymphocyte function-associated antigen 1 become autoreactive and cause a lupuslike disease in syngeneic mice. J Clin Invest 1996; 97: 2866-71.PubMedGoogle Scholar
  99. 99.
    Rao T, Richardson B: Environmentally induced autoimmune diseases: potential mechanisms. Environ Health Perspect 1999; 107 Suppl 5: 737-42.PubMedGoogle Scholar
  100. 100.
    Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, Bird A: Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 1998; 393: 386-9.PubMedGoogle Scholar
  101. 101.
    Leoni F, Fossati G, Lewis EC, Lee JK, Porro G, Pagani P, Modena D, Moras ML, Pozzi P, Reznikov LL, Siegmund B, Fantuzzi G, Dinarello CA, Mascagni P: The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo. Mol Med 2005; 11: 1-15.PubMedGoogle Scholar
  102. 102.
    Glauben R, Batra A, Fedke I, Zeitz M, Lehr HA, Leoni F, Mascagni P, Fantuzzi G, Dinarello CA, Siegmund B: Histone hyperacetylation is associated with amelioration of experimental colitis in mice. J Immunol 2006; 176: 5015-22.PubMedGoogle Scholar
  103. 103.
    Leng C, Gries M, Ziegler J, Lokshin A, Mascagni P, Lentzsch S, Mapara MY: Reduction of graft-versus-host disease by histone deacetylase inhibitor suberonylanilide hydroxamic acid is associated with modulation of inflammatory cytokine milieu and involves inhibition of STAT1. Exp Hematol 2006; 34: 776-87.PubMedGoogle Scholar
  104. 104.
    Pietsch P, Vohr HW, Degitz K, Gleichmann E: Immunopathological signs inducible by mercury compounds. II. HgCl2 and gold sodium thiomalate enhance serum IgE and IgG concentrations in susceptible mouse strains. Int. Arch. Allergy Appl. Immun. 1989; 90: 47-53.Google Scholar
  105. 105.
    Ochel M, Vohr H-W, Pfeiffer C, Gleichmann E: IL-4 is required for the IgE and IgG1 increase and IgG1 autoantibody formation in mice treated with mercuric chloride. J. Immunol. 1991; 146: 3006-11.PubMedGoogle Scholar
  106. 106.
    Haggqvist B, Hultman P: Effects of deviating the Th2-response in murine mercury-induced autoimmunity towards a Th1-response. Clin Exp Immunol 2003; 134: 202-9.PubMedGoogle Scholar
  107. 107.
    Biancone L, Andres G, Ahn H, Lim A, Dai C, Noelle R, Yagita H, De Martino C, Stamenkovic I: DistincTregulatory roles of lymphocyte costimulatory pathways on T helper type 2-mediated autoimmune disease. J. Exp. Med. 1996; 183: 1473-1481.PubMedGoogle Scholar
  108. 108.
    Zheng Y, Jost M, Gaughan JP, Class R, Coyle AJ, Monestier M: ICOS-B7 homologous protein interactions are necessary for mercury- induced autoimmunity. J Immunol 2005; 174: 3117-21.PubMedGoogle Scholar
  109. 109.
    Zheng Y, Monestier M: Inhibitory signal override increases susceptibility to mercury-induced autoimmunity. J Immunol 2003; 171: 1596-601.PubMedGoogle Scholar
  110. 110.
    Layland LE, Wulferink M, Dierkes S, Gleichmann E: Drug-induced autoantibody formation in mice: triggering by primed CD4+CD25- T cells, prevention by primed CD4+CD25+ T cells. Eur J Immunol 2004; 34: 36-46.PubMedGoogle Scholar
  111. 111.
    Kiely PD, Pecht I, Oliveira DB: Mercuric chloride-induced vasculitis in the Brown Norway rat: alpha beta T cell-dependent and -independent phases: role of the mast cell. J Immunol 1997; 159: 5100-6.PubMedGoogle Scholar
  112. 112.
    Vinen CS, Turner DR, Oliveira DB: A central role for the mast cell in early phase vasculitis in the Brown Norway rat model of vas- culitis: a histological study. Int J Exp Pathol 2004; 85: 165-74.PubMedGoogle Scholar
  113. 113.
    Badou A, Saoudi A, Dietrich G, Druet E, Druet P, Pelletier L: Mercuric chloride-induced autoimmunity. Curr. Prot. Immunol. 1999; 15: 1-18.Google Scholar
  114. 114.
    Tournade H, Pelletier L, Pasquier R, Vial M-C, Mandet C, Druet P: D-penicillamine-induced autoimmunity in Brown Norway rats: similarities with HgCl2-induced autoimmunity. J. Immunol. 1990; 144: 2985-2991.PubMedGoogle Scholar
  115. 115.
    Tournade H, Pelletier L, Guéry JC, Pasquier R, Nochy D, Hinglais N, Guilbert B, Druet P: Experimental gold-induced autoimmunity. Nephrol. Dial. Transplant. 1991; 6: 621-630.PubMedGoogle Scholar
  116. 116.
    Mathieson PW, Stapleton KJ, Oliveira DBG, Lockwood CM: Immunoregulation of mercuric chloride-induced autoimmunity in Brown Norway rats: a role for CD8+ T cells revealed by in vivo depletion studies. Eur. J. Immunol. 1991; 21: 2105-9.PubMedGoogle Scholar
  117. 117.
    Field AC, Bloch MF, Bellon B: Neonatal tolerance to a Th2-mediated autoimmune disease generates CD8+ Tc1 regulatory cells. J Autoimmun 2003; 21: 201-12.PubMedGoogle Scholar
  118. 118.
    Masson MJ, Uetrecht JP: Tolerance induced by low dose D-penicillamine in the brown Norway rat model of drug-induced au- toimmunity is immune-mediated. Chem Res Toxicol 2004; 17: 82-94.PubMedGoogle Scholar
  119. 119.
    Seguin B, Masson MJ, Uetrecht J: D-penicillamine-induced autoimmunity in the Brown Norway rat: role for both T and non-T splenocytes in adoptive transfer of tolerance. Chem Res Toxicol 2004; 17: 1299-302.PubMedGoogle Scholar
  120. 120.
    Bridoux F, Badou A, Saoudi A, Bernard I, Druet E, Pasquier R, Druet P, Pelletier L: TGF-b dependent inhibition of Th2-induced autoimmunity by self MHC class II specific, regulatory CD4+ T cell lines. J. Exp. Med. 1997; 185: 1769-1775PubMedGoogle Scholar
  121. 121.
    Qasim FJ, Thiru S, Mathieson PW, Oliveira DB: The time course and characterization of mercuric chloride-induced immunopathol- ogy in the brown Norway rat. J. Autoimmun. 1995; 8: 193-208.PubMedGoogle Scholar
  122. 122.
    Wu Z, Turner DR, Oliveira DB: Antioxidants inhibit mercuric chloride-induced early vasculitis. Int Immunol 2002; 14: 267-73.PubMedGoogle Scholar
  123. 123.
    Wu Z, Turner DR, Oliveira DB: IL-4 gene expression up-regulated by mercury in rat mast cells: a role of oxidant stress in IL-4 transcription. Int Immunol 2001; 13: 297-304.PubMedGoogle Scholar
  124. 124.
    Wu Z, MacPhee IA, Oliveira DB: Reactive oxygen species in the initiation of IL-4 driven autoimmunity as a potential therapeutic target. Curr Pharm Des 2004; 10: 899-913.PubMedGoogle Scholar
  125. 125.
    Fillion J, Baccala R, Kuhn J, Druet P, Bellon B: Evidence for heterogenous TCRVb expression in mercury-induced autoimmune disorders in rats. Int. Immunol. 1997; 9: 263-271.PubMedGoogle Scholar
  126. 126.
    Badou A, Savignac M, Moreau M, Leclerc C, Pasquier R, Druet P, Pelletier L: HgCl2-induced IL-4 gene expression in T cells involves protein kinase C-dependent calcium influx through L-type calcium channels. J. Biol. Chem. 1997; 272: 32411-8.PubMedGoogle Scholar
  127. 127.
    Savignac M, Badou A, Moreau M, Leclerc C, Guery JC, Paulet P, Druet P, Ragab-Thomas J, Pelletier L: Protein kinase C-mediated calcium entry dependent upon dihydropyridine sensitive channels: a T cell receptor-coupled signaling pathway involved in IL-4 synthesis. Faseb J 2001; 15: 1577-9.PubMedGoogle Scholar
  128. 128.
    Prigent P, Saoudi A, Pannetier C, Graber P, Bonnefoy Y, Druet P, Hirsch F: Mercuric chloride, a chemical responsible for Th2-medi- ated autoimmunity in Brown-Norway rats, directly triggers T cells to produce IL-4. J. Clin. Invest. 1995; 96: 1484-9.PubMedGoogle Scholar
  129. 129.
    Savignac M, Gomes B, Gallard A, Narbonnet S, Moreau M, Leclerc C, Paulet P, Mariame B, Druet P, Saoudi A, Fournie GJ, Guery JC, Pelletier L: Dihydropyridine receptors are selective markers of Th2 cells and can be targeted to prevent Th2-dependent im- munopathological disorders. J Immunol 2004; 172: 5206-12.PubMedGoogle Scholar
  130. 130.
    Gomes B, Savignac M, Cabral MD, Paulet P, Moreau M, Leclerc C, Feil R, Hofmann F, Guery JC, Dietrich G, Pelletier L: The cGMP/pro- tein kinase G pathway contributes to dihydropyridine-sensitive calcium response and cytokine production in TH2 lymphocytes. J Biol Chem 2006; 281: 12421-7.PubMedGoogle Scholar
  131. 131.
    Pelletier L, Pasquier R, Rossert J, Vial M-C, Mandet C, Druet P: Autoreactive T cells in mercury-induced autoimmunity. Ability to induce the autoimmune disease. J. Immunol. 1988; 140: 750-4.PubMedGoogle Scholar
  132. 132.
    Erb KJ, Ruger B, von Brevern M, Ryffel B, Schimpl A, Rivett K: Constitutive expression of interleukin (IL)-4 in vivo causes autoim- mune- type disorders in mice. J Exp Med 1997; 185: 329-39.PubMedGoogle Scholar
  133. 133.
    Rossert J, Pelletier L, Pasquier R, Druet P: Autoreactive T cells in mercury-induced autoimmunity. Demonstration by limiting dilution analysis. Eur. J. Immunol. 1988; 18: 1761-1766.PubMedGoogle Scholar
  134. 134.
    Saoudi A, Castedo M, Nochy D., Mandet C, Pasquier R, Druet P, Pelletier L: Self reactive anti-class II Th2 cell lines derived from gold salt-injected rats trigger B cell polyclonal activation and transfer autoimmunity in CD8-depleted normal syngeneic recipients. Eur. J. Immunol. 1995; 25: 1972-1979.PubMedGoogle Scholar
  135. 135.
    Roos A, Claessen N, Weening JJ, Aten J: Enhanced T lymphocyte expression of LFA-1, ICAM-1, and the TNF receptor family member OX40 in HgCl2-induced systemic autoimmunity. Scand J Immunol 1996; 43: 507-18.PubMedGoogle Scholar
  136. 136.
    Croft MA, Kaufman PL: Accommodation and presbyopia: the ciliary neuromuscular view. Ophthalmol Clin North Am 2006; 19: 13-24, v.PubMedGoogle Scholar
  137. 137.
    Field AC, Caccavelli L, Fillion J, Kuhn J, Mandet C, Druet P, Bellon B: Neonatal induction of tolerance to T(h)2-mediated autoim- munity in rats. Int Immunol 2000; 12: 1467-77.PubMedGoogle Scholar
  138. 138.
    Field AC, Caccavelli L, Bloch MF, Bellon B: Regulatory CD8+ T cells control neonatal tolerance to a Th2-mediated autoimmunity. J Immunol 2003; 170: 2508-15.PubMedGoogle Scholar
  139. 139.
    Nomura T, Sakaguchi S: Foxp3 and Aire in thymus-generated T(reg) cells: a link in self-tolerance. Nat Immunol 2007; 8: 333-4.PubMedGoogle Scholar
  140. 140.
    Flint J, Mott R: Finding the molecular basis of quantitative traits: successes and pitfalls. Nat Rev Genet 2001; 2: 437-45.PubMedGoogle Scholar
  141. 141.
    Hemminki K, Lorenzo Bermejo J, Forsti A: The balance between heritable and environmental aetiology of human disease. Nat Rev Genet 2006; 7: 958-65.PubMedGoogle Scholar
  142. 142.
    Johnston PG, Lenz HJ, Leichman CG, Danenberg KD, Allegra CJ, Danenberg PV, Leichman L: Thymidylate synthase gene and protein expression correlate and are associated with response to 5-fluorouracil in human colorectal and gastric tumors. Cancer Res 1995; 55: 1407-12.PubMedGoogle Scholar
  143. 143.
    Antignac C: Genetic models: clues for understanding the pathogenesis of idiopathic nephrotic syndrome. J Clin Invest 2002; 109: 447-9.PubMedGoogle Scholar
  144. 144.
    Antignac C: Molecular basis of steroid-resistant nephrotic syndrome. Nefrologia 2005; 25 Suppl 2: 25-8.PubMedGoogle Scholar
  145. 145.
    Sternberg SS: Cross-striated fibrils and other ultrastructural alterations in glomeruli of rats with daunomycin nephrosis. Lab Invest 1970; 23: 39-51.PubMedGoogle Scholar
  146. 146.
    Bertani T, Rocchi G, Sacchi G, Mecca G, Remuzzi G: Adriamycin-induced glomerulosclerosis in the rat. Am J Kidney Dis 1986; 7: 12-9.PubMedGoogle Scholar
  147. 147.
    Fogo AB: Animal models of FSGS: lessons for pathogenesis and treatment. Semin Nephrol 2003; 23: 161-71.PubMedGoogle Scholar
  148. 148.
    Zheng Z, Schmidt-Ott KM, Chua S, Foster KA, Frankel RZ, Pavlidis P, Barasch J, D’Agati VD, Gharavi AG: A Mendelian locus on chromosome 16 determines susceptibility to doxorubicin nephropathy in the mouse. Proc Natl Acad Sci U S A 2005; 102: 2502-7.PubMedGoogle Scholar
  149. 149.
    Zheng Z, Pavlidis P, Chua S, D’Agati VD, Gharavi AG: An ancestral haplotype defines susceptibility to doxorubicin nephropathy in the laboratory mouse. J Am Soc Nephrol 2006; 17: 1796-800.PubMedGoogle Scholar
  150. 150.
    Tournade H, Guéry J-C, Pasquier R, Vial MC, Mandet C, Druet E, Dansette PM, Druet P, Pelletier L: Effect of the thiol group on experimental gold-induced autoimmunity. Arthritis Rheum. 1991; 34: 1594-1599.PubMedGoogle Scholar
  151. 151.
    Gold therapy in rheumatoid arthritis-final report of a multi-centre controlled trial. Empire Rheumatism Council. Ann Rheum Dis 1961; 20: 315-334.Google Scholar
  152. 152.
    Fillastre JP, Mery JP, Druet P: [Drug-induced glomerular nephropathies]. Nephrologie 1983; 4: 1-9.PubMedGoogle Scholar
  153. 153.
    Sapin C, Druet E, Druet P: Induction of anti-glomerular basement antibodies in the Brown-Norway rat by mercuric chloride. Clin. Exp. Immunol. 1977; 28: 173-178.PubMedGoogle Scholar
  154. 154.
    Druet E, Sapin C, Günther E, Feingold N, Druet P: Mercuric chloride-induced anti-glomerular basement membrane antibodies in the rat. Genetic control. Eur J Immunol 1977; 7: 348-351.PubMedGoogle Scholar
  155. 155.
    Fournie GJ, Cautain B, Xystrakis E, Damoiseaux J, Mas M, Lagrange D, Bernard I, Subra JF, Pelletier L, Druet P, Saoudi A: Cellular and genetic factors involved in the difference between Brown Norway and Lewis rats to develop respectively type-2 and type-1 immune-mediated diseases. Immunol Rev 2001; 184: 145-60.PubMedGoogle Scholar
  156. 156.
    Cautain B, Damoiseaux J, Bernard I, Xystrakis E, Fournie E, van Breda Vriesman P, Druet P, Saoudi A: The CD8 T cell compartment plays a dominant role in the deficiency of Brown-Norway rats to mount a proper type 1 immune response. J Immunol 2002; 168: 162-70.PubMedGoogle Scholar
  157. 157.
    Subra JF, Cautain B, Xystrakis E, Mas M, Lagrange D, van Der Heijden H, van De Gaar MJ, Druet P, Fournie GJ, Saoudi A, Damoiseaux J: The balance between CD45RC(high) and CD45RC(low) CD4 T cells in rats is intrinsic to bone marrow-derived cells and is genetically controlled. J Immunol 2001; 166: 2944-52.PubMedGoogle Scholar
  158. 158.
    Xystrakis E, Cavailles P, Dejean AS, Cautain B, Colacios C, Lagrange D, van de Gaar MJ, Bernard I, Gonzalez-Dunia D, Damoiseaux J, Fournie GJ, Saoudi A: Functional and genetic analysis of two CD8 T cell subsets defined by the level of CD45RC expression in the rat. J Immunol 2004; 173: 3140-7.PubMedGoogle Scholar
  159. 159.
    Kermarrec N, Dubay C, De Gouyon B, Blanpied C, Gauguier D, Gillespie K, Druet P, Lathrop M, Hirsch F: Serum IgE concentration and other immune manifestations of treatment with gold salts are linked to MHC and IL-4 regions in the rat. Genomics 1996; 31: 111-4.PubMedGoogle Scholar
  160. 160.
    Mas M, Cavailles P, Colacios C, Subra JF, Lagrange D, Calise M, Christen MO, Druet P, Pelletier L, Gauguier D, Fournie GJ: Studies of congenic lines in the Brown Norway rat model of Th2-mediated immunopathological disorders show that the aurothiopropanol sulfonate-induced immunological disorder (Aiid3) locus on chromosome 9 plays a major role compared to Aiid2 on chromosome 10. J Immunol 2004; 172: 6354-61.PubMedGoogle Scholar
  161. 161.
    Mas M, Subra JF, Lagrange D, Pilipenko-Appolinaire S, Kermarrec N, Gauguier D, Druet P, Fournie GJ: Rat chromosome 9 bears a major susceptibility locus for IgE response. Eur J Immunol 2000; 30: 1698-705.PubMedGoogle Scholar
  162. 162.
    Damoiseaux JG, Cautain B, Bernard I, Mas M, van Breda Vriesman PJ, Druet P, Fournie G, Saoudi A: A dominant role for the thymus and MHC genes in determining the peripheral CD4/CD8 T cell ratio in the rat. J. Immunol. 1999; 163: 2983-2989.PubMedGoogle Scholar
  163. 163.
    Frazer KA, Ueda Y, Zhu Y, Gifford VR, Garofalo MR, Mohandas N, Martin CH, Palazzolo MJ, Cheng JF, Rubin EM: Computational and biological analysis of 680 kb of DNA sequence from the human 5q31 cytokine gene cluster region. Genome Res 1997; 7: 495-512.PubMedGoogle Scholar
  164. 164.
    Marsh DG, Neely JD, Breazeale DR, Ghosh B, Freidhoff LR, Schou C, Beaty TH: Genetic basis of IgE responsiveness: relevance to the atopic diseases. Int Arch Allergy Immunol 1995; 107: 25-8.PubMedGoogle Scholar
  165. 165.
    Meyers DA, Postma DS, Panhuysen CIM, Xu J, Amelung PJ, Levitt RC, Bleekers ER: Evidence for a locus regulating total serum IgE levels mapping to chromosome 5. Genomics 1994; 23: 464-70.PubMedGoogle Scholar
  166. 166.
    Gorham JD, Guler ML, Steen RG, Mackey AJ, Daly MJ, Frederick K, Dietrich WF, Murphy KM: Genetic mapping of a murine locus controlling development of T helper 1/T helper 2 type responses. Proc. Natl. Acad. Sci. USA 1996; 93: 12467-12472.PubMedGoogle Scholar
  167. 167.
    Guler ML, Gorham JD, Dietrich WF, Murphy TL, Steen RG, Parvin CA, Fenoglio D, Grupe A, Peltz G, Murphy KM: Tpm1, a locus controlling IL-12 responsiveness, acts by a cell- autonomous mechanism. J Immunol 1999; 162: 1339-47.PubMedGoogle Scholar
  168. 168.
    Dahlman I, Wallstrom E, Weissert R, Storch M, Kornek B, Jacobsson L, Linington C, Luthman H, Lassmann H, Olsson T: Linkage analysis of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in the rat identifies a locus controlling demyelination on chromosome 18. Hum Mol Genet 1999; 8: 2183-90.PubMedGoogle Scholar
  169. 169.
    Roth MP, Viratelle C, Dolbois L, Delverdier M, Borot N, Pelletier L, Druet P, Clanet M, Coppin H: A genome-wide search identifies two susceptibility loci for experimental autoimmune encephalomyelitis on rat chromosomes 4 and 10. J. Immunol. 1999; 162: 1917-1922.PubMedGoogle Scholar
  170. 170.
    Williams RM, Moore MJ: Linkage of susceptibility to experimental allergic encephalomyelitis to the major histocompatibility locus in the rat. J Exp Med 1973; 138: 775-83.PubMedGoogle Scholar
  171. 171.
    Furuya T, Salstrom JL, McCall-Vining S, Cannon GW, Joe B, Remmers EF, Griffiths MM, Wilder RL: Genetic dissection of a rat model for rheumatoid arthritis: significant gender influences on autosomal modifier loci. Hum Mol Genet 2000; 9: 2241-50.PubMedGoogle Scholar
  172. 172.
    Powrie F, Mason D: Subsets of rat CD4+ T cells defined by their differential expression of variants of the CD45 antigen: developmental relationships and in vitro and in vivo functions. Curr Top Microbiol Immunol 1990; 159: 79-96.PubMedGoogle Scholar
  173. 173.
    Fowell D, McKnight AJ, Powrie F, Dyke R, Mason D: Subsets of CD4+ T cells and their role in the induction and prevention of autoimmunity. Immunol. Rev. 1991; 123: 37-64.PubMedGoogle Scholar
  174. 174.
    McKnight AJ, Barclay AN, Mason DW: Molecular cloning of rat interleukine 4 cDNA and analysis of the cytokine repertoire of subsets of CD4+ T cells. Eur. J. Immunol. 1991; 21: 1187-94.PubMedGoogle Scholar
  175. 175.
    Rogner UC, Avner P: Congenic mice: cutting tools for complex immune disorders. Nat Rev Immunol 2003; 3: 243-52.PubMedGoogle Scholar
  176. 176.
    Aitman TJ, Glazier AM, Wallace CA, Cooper LD, Norsworthy PJ, Wahid FN, Al-Majali KM, Trembling PM, Mann CJ, Shoulders CC, Graf D, St Lezin E, Kurtz TW, Kren V, Pravenec M, Ibrahimi A, Abumrad NA, Stanton LW, Scott J: Identification of Cd36 (Fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats. Nat Genet 1999; 21: 76-83.PubMedGoogle Scholar
  177. 177.
    Olofsson P, Holmberg J, Tordsson J, Lu S, Akerstrom B, Holmdahl R: Positional identification of Ncf1 as a gene thaTregulates arthritis severity in rats. Nat Genet 2003; 33: 25-32.PubMedGoogle Scholar
  178. 178.
    Rozzo SJ, Allard JD, Choubey D, Vyse TJ, Izui S, Peltz G, Kotzin BL: Evidence for an interferon-inducible gene, Ifi202, in the suscep- tibility to systemic lupus. Immunity 2001; 15: 435-43.PubMedGoogle Scholar
  179. 179.
    Backdahl L, Ribbhammar U, Lorentzen JC: Mapping and functional characterization of rat chromosome 4 regions that regulate arthritis models and phenotypes in congenic strains. Arthritis Rheum 2003; 48: 551-9.PubMedGoogle Scholar
  180. 180.
    Hattori M, Yamato E, Itoh N, Senpuku H, Fujisawa T, Yoshino M, Fukuda M, Matsumoto E, Toyonaga T, Nakagawa I, Petruzzelli M, McMurray A, Weiner H, Sagai T, Moriwaki K, Shiroishi T, Maron R, Lund T: Cutting edge: homologous recombination of the MHC class I K region defines new MHC-linked diabetogenic susceptibility gene(s) in nonobese diabetic mice. J Immunol 1999; 163: 1721-4.PubMedGoogle Scholar
  181. 181.
    Morel L, Blenman KR, Croker BP, Wakeland EK: The major murine systemic lupus erythematosus susceptibility locus, Sle1, is a cluster of functionally related genes. Proc Natl Acad Sci U S A 2001; 98: 1787-92.PubMedGoogle Scholar
  182. 182.
    Podolin PL, Denny P, Lord CJ, Hill NJ, Todd JA, Peterson LB, Wicker LS, Lyons PA: Congenic mapping of the insulin-dependent diabetes (Idd) gene, Idd10, localizes two genes mediating the Idd10 effect and eliminates the candidate Fcgr1. J Immunol 1997; 159: 1835-43.PubMedGoogle Scholar
  183. 183.
    Eisen MB, Spellman PT, Brown PO, Botstein D: Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A 1998; 95: 14863-8.PubMedGoogle Scholar
  184. 184.
    Harley JB, Moser KL, Gaffney PM, Behrens TW: The genetics of human systemic lupus erythematosus. Curr Opin Immunol 1998; 10: 690-6.PubMedGoogle Scholar
  185. 185.
    Walley AJ, Wiltshire S, Ellis CM, Cookson WO: Linkage and allelic association of chromosome 5 cytokine cluster genetic markers with atopy and asthma associated traits. Genomics 2001; 72: 15-20.PubMedGoogle Scholar
  186. 186.
    Gerber BO, Pichler WJ: Noncovalent interactions of drugs with immune receptors may mediate drug-induced hypersensitivity reactions. Aaps J 2006; 8: E160-5.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Lucette Pelletier
    • 1
  • Abdelhadi Saoudi
    • 1
  • Gilbert Fournié
    • 1
  1. 1.INSER U563, Centre de Physiopathologie Toulouse PurpanToulouse cedex 3France

Personalised recommendations