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Autoreactive T cells in murine lupus

Origins and Roles in Autoantibody Production

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Abstract

The conventional paradigm to explain systemic lupus erythematosus (SLE) is that disease results from tissue deposition of pathogenic autoantibodies and immune complexes, secondary to activation of autoreactive B cells in the context of help from αΒ T cells. Recent work in murine lupus has confirmed this notion and demonstrated that autoantigen-specific αΒ T cells are absolutely required for full penetrance of disease, with such autoreactive αΒ T cells, even in Fasintact mice, likely arising from defects in peripheral tolerance. These studies have also revealed a network of regulation that also involves nonclassical pathogenic and downregulatory αΒ and γδ T cells, suggesting that the lupus immune system involves more complex interactions than the conventional paradigm suggests.

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References

  1. Tan EM: Antinuclear antibodies: Diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol 1989;44: 93–151.

    PubMed  CAS  Google Scholar 

  2. Theofilopoulos AN, Dixon FJ: Murine models of systemic lupus erythematosus. Adv Immunol 1985;37:269–390.

    PubMed  CAS  Google Scholar 

  3. Eisenberg RA, Tan EM, Dixon FJ: Presence of anti-Sm reactivity in autoimmune mouse strains. J Exp Med 1978;147:582–587.

    Article  PubMed  CAS  Google Scholar 

  4. Hewicker M, Trautwein G:Glomerular lesions in MRL mice. A light and immunofluorescence microscopic study. Zentralblatt für Veterinarmedizin Reihe B 1986;33:727–739.

    CAS  Google Scholar 

  5. Burlingame RW, Rubin RL, Balderas RS, Theofilopoulos AN: Genesis and evolution of antichromatin autoantibodies in murine lupus implicates T-dependent immunization with self antigen. J Clin Invest 1993;91: 1687–1696.

    PubMed  CAS  Google Scholar 

  6. Fatenejad S, Brooks W, Schwartz A, Craft J: Pattern of anti-small nuclear ribonucleoprotein antibodies in MRL/Mp-lpr/lpr mice suggests that the intact U1 snRNP particle is their autoimmunogenic target. J Immunol 1994; 152: 5523–5531.

    PubMed  CAS  Google Scholar 

  7. Rathmell JC, Goodnow CC:Effects of the lpr mutation on elimination and inactivation of self-reactive B cells. J Immunol 1994;153: 2831–2842.

    PubMed  CAS  Google Scholar 

  8. Singer GG, Abbas AK: The fas antigen is involved in peripheral but not thymic deletion of T lymphocytes in T cell receptor transgenic mice. Immunity 1994;1:365–371.

    Article  PubMed  CAS  Google Scholar 

  9. Van Parijs L, Ibraghimov A, Abbas AK: The roles of costimulation and fas in T cell apoptosis and peripheral tolerance. Immunity 1996;4:321–328.

    Article  PubMed  Google Scholar 

  10. Izui S, Kelley VE, Masuda K, Yoshida H, Roths JB, Murphy ED: Induction of various autoantibodies by mutant genelpr in several strains of mice. J Immunol 1984; 133:227–233.

    PubMed  CAS  Google Scholar 

  11. Peng SL, Craft J: The regulation of murine lupus. Ann NY Acad Sci 1997;815:128–138.

    Article  PubMed  CAS  Google Scholar 

  12. Craft J, Fatenejad S: Self antigens and epitope spreading in systemic autoimmunity. Arthritis Rheum 1997;40:1374–1382.

    Article  PubMed  CAS  Google Scholar 

  13. Hardin JA: The lupus autoantigens and the pathogenesis of systemic lupus erythematosus. Arthritis Rheum 1986;29:457–460.

    Article  PubMed  CAS  Google Scholar 

  14. Shlomchik MJ, Marshak-Rothstein A, Wolfowicz CB, Rothstein TL, Weigert MG: The role of clonal selection and somatic mutation in autoimmunity. Nature 1987;328: 805–811.

    Article  PubMed  CAS  Google Scholar 

  15. Eilat D, Webster DM, Rees AR: V region sequences of anti-DNA and anti-RNA autoantibodies from NZB/NZW F1 mice. J Immunol 1988;141:1745–1743.

    PubMed  CAS  Google Scholar 

  16. Shlomchik MJ, Mascelli M, Shan H, Radic MZ, Pisetsky D, Marshak-Rothstein A, et al.: Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. J Exp Med 1990;171: 265–273.

    Article  PubMed  CAS  Google Scholar 

  17. Marion TN, Tillman DM, Jou N: Interclonal and intraclonal diversity among anti-DNA antibodies from an (NZB x NZW)F1 mouse. J Immunol 1990;145:2322–2332.

    PubMed  CAS  Google Scholar 

  18. O’Keefe TL, Bandyopadhyay S, Datta SK, Imanishi-Kari T: V region sequences of an idiotypically connected family of pathogenic anti-DNA autoantibodies. J Immunol 1990; 144:4275–4283.

    Google Scholar 

  19. Davidson A, Mannheimer-Lory A, Aranow C, Peterson R, Hannigan N, Diamond B: Molecular characterization of a somatically mutated anti-DNA antibody bearing two SLE related idiotypes. J Clin Invest 1990;85:1401–1409.

    Article  PubMed  CAS  Google Scholar 

  20. Diamond B, Katz JB, Paul E, Aranow C, Lustgarten D, Scharff MD: The role of somatic mutation in the pathogenic anti-DNA response. Annu Rev Immunol 1992;10:731–757.

    Article  PubMed  CAS  Google Scholar 

  21. Radic MZ, Weigert M: Genetic and structural evidence for antigen selection of anti-DNA antibodies. Annu Rev Immunol 1994; 12:487–520.

    Article  PubMed  CAS  Google Scholar 

  22. Steinberg AD, Roths JB, Murphy ED, Steinberg RT, Raveche ES: Effects of thymectomy or androgen administration upon the autoimmune disease of MRL/Mp-lpr/ lpr mice. J Immunol 1980; 125: 871–873.

    PubMed  CAS  Google Scholar 

  23. Wofsy DL, Ledbetter JA, Hendler PL, Seaman WE: Treatment of murine lupus with monoclonal anti-T cell antibody. J Immunol 1985;134:852.

    PubMed  CAS  Google Scholar 

  24. Santoro TJ, Portanova JP, Kotzin BL: The contribution of L3T4+ T cells to lymphoproliferation and autoantibody production in MRL-lpr/lpr mice. J Exp Med 1988; 167:1713–1718.

    Article  PubMed  CAS  Google Scholar 

  25. Sobel ES, Cohen PL, Eisenberg RA: lpr T cells are necessary for autoantibody production in lpr mice. J Immunol 1993;150: 4160–4167.

    PubMed  CAS  Google Scholar 

  26. Philpott KL, Viney JL, Kay G, Rastan S, Gardiner EM, Chae S, et al.: Lymphoid development in mice congenitally lacking T cell receptor alpha beta-expressing cells. Science 1992;256:1448–1452.

    Article  PubMed  CAS  Google Scholar 

  27. Peng SL, Madaio MP, Hughes DPM, Crispe I, Owen M, Wen L, Hayday A, Craft J: Murine lupus in the absence of αΒ T cells. J Immunol 1996;156:4041–4049.

    PubMed  CAS  Google Scholar 

  28. Jevnikar AM, Grusby MJ, Glimcher LH: Prevention of nephritis in major histocompatibility complex class II-deficient MRL-lpr mice. J Exp Med 1994;179:1137–1143.

    Article  PubMed  CAS  Google Scholar 

  29. Koh D-R, Ho A, Rahemutulla A, Fung-Leung W-P, Griesser H, Mak T-W: Murine lupus in MRL/lpr mice lacking CD4 or CD8 T cells. Eur J Immunol 1995;25: 2558–2562.

    Article  PubMed  CAS  Google Scholar 

  30. Giese T, Davidson WF: Chronic treatment of C3H-lpr/lpr and C3H-gld/gld mice, with anti-CD8 monoclonal antibody prevent the accumulation of double negative T cells but not autoantibody production. J Immunol 1994; 152: 2000.

    PubMed  CAS  Google Scholar 

  31. Giese T, Davidson WF: CD8+ T cell-deficientlpr/lpr mice, CD4+ B220+ and CD4+B220. T cells replace B220+ double-negative T cells as the predominant populations in enlarged lymph nodes. J Immunol 1995;154: 4986–4995.

    PubMed  CAS  Google Scholar 

  32. Maldonado MA, Eisenberg RA, Roper E, Cohen PL, Kotzin BL: Greatly reduced lymphoproliferation inlpr mice lacking major histocompatibility complex class I J Exp Med 1995;181:641–648.

    Article  PubMed  CAS  Google Scholar 

  33. Mixter PF, Russell JQ, Durie FH, Budd RC: Decreased CD4-CD8- TCR-αΒ+ cells inlpr/lpr mice lacking Β2-microglobulin. J Immunol 1995;154:2063–2074.

    PubMed  CAS  Google Scholar 

  34. Ohteki T, Iwamoto M, Izui S, MacDonald HR: Reduced development of CD4-8-B220+ T cells but normal autoantibody production inlpr/lpr mice lacking major histocompatibility complex class I molecules. Eur J Immunol 1995; 25:37–41.

    Article  PubMed  CAS  Google Scholar 

  35. Adams S, Leblanc P, Datta SK: Junctional region sequences of T-cell receptor beta-chain genes expressed by pathogenic anti-DNA autoantibody-inducing helper T cells from lupus mice: possible selection by cationic autoantigens. PNAS 1991;88:11,271–11,275.

    CAS  Google Scholar 

  36. Mohan C, Adams S, Stanik V, Datta SK: Nucleosome: a major immunogen for pathogenic autoantibodyinducing T cells of lupus. J Exp Med 1993;177: 1367–1381.

    Article  PubMed  CAS  Google Scholar 

  37. Kaliyaperumal A, Mohan C, Wu W, Datta SK: Nucleosomal peptide epitopes for nephritis-inducing T helper cells of murine lupus. J Exp Med 1996;183:2459–2469.

    Article  PubMed  CAS  Google Scholar 

  38. Sobel ES, Kakkanaiah VN, Kakkanaiah M, Cheek RL, Cohen PL, Eisenberg RA: T-B collaboration for autoantibody production in lpr mice is cognate and MHC-restricted. J Immunol 1994;152: 6011–6016.

    PubMed  CAS  Google Scholar 

  39. Ma J, Xu J, Peng Q, Zhang J, Grewal IS, Flavell RA, Craft J: Autoimmunelpr/lpr mice deficient in CD40 ligand: spontaneous immunoglobulin class switching with dichotomy of autoantibody responses. J Immunol 1996;157: 417–426.

    PubMed  CAS  Google Scholar 

  40. Finck BK, Linsley PS, Wofsy D: Treatment of murine lupus with CTLA4Ig. Science 1994;265: 1225–1227.

    Article  PubMed  CAS  Google Scholar 

  41. Mohan C, Shi Y, Laman JD, Datta SK: Interaction between CD40 and its ligand gp39 in the development of murine lupus nephritis. J Immunol 1995;154:1470–1480.

    PubMed  CAS  Google Scholar 

  42. Kaye J, Hsu ML, Sauron ME, Jameson SC, Gascoigne NR, Hedrick SM: Selective development of CD4+ T cells in transgenic mice expressing a class II MHC-restricted antigen receptor. Nature 1989;341:746–749.

    Article  PubMed  CAS  Google Scholar 

  43. Peng SL, Fatenejad S, Craft J: Induction of non-pathologic, humoral autoimmunity in lupus-prone mice by a class II-restricted, transgenic αΒ T cell: separation of autoantigen-specific and -nonspecific help. J Immunol 1996; 157: 5225–5230.

    PubMed  CAS  Google Scholar 

  44. Desai-Mehta A, Lu L, Ramsey GR, Datta SK: Hyperexpression of CD40 ligand by B and T cells in human lupus and its role in pathogenic autoantibody production. J Clin Invest 1996;97:2063–2073.

    Article  PubMed  CAS  Google Scholar 

  45. Desai-Mehta A, Mao C, Rajagopalan S, Robinson T, Datta SK: Structure and specificity of T cell receptors expressed by potentially pathogenic anti-DNA autoantibodyinducing T cells in human lupus. J Clin Invest 1995;95:531–541.

    PubMed  CAS  Google Scholar 

  46. Koshy M, Berger D, Crow MK: Increased expression of CD40 ligand on systemic lupus erythematosus lymphocytes. J Clin Invest 1996;98:826–837.

    PubMed  CAS  Google Scholar 

  47. Hoffman RW, Takeda Y, Sharp GC, Lee DR, Hill DL, Kaneoka H, et al.: Human T cell clones reactive against U-small nuclear ribonucleoprotein autoantigens from connective tissue disease patients and healthy individuals. J Immunol 1993;151:6460.

    PubMed  CAS  Google Scholar 

  48. Okubo M, Yamamoto K, Kato T, Matsuuraa N, Nishimaki T, Kasukawa R, et al.: Detection and epitope analysis of autoantigen-reactive T cells to the U1-small nuclear ribonucleoprotein A protein in autoimmune disease patients. J Immunol 1993;151: 1108–1115.

    PubMed  CAS  Google Scholar 

  49. Eisenberg R, Dyer K, Craven SY, Fuller CR, Yount W: Subclass restriction and polyclonality of the systemic lupus erythematosus marker antibody anti-Sm. J Clin Invest 1985;75:1270.

    PubMed  CAS  Google Scholar 

  50. Crow MK, DelGiudice-Asch G, Zehetbauer JB, Lawson JL, Brot N, Weissbach H, et al.: Autoantigen-specific T cell proliferation induced by the ribosomal P2 protein in patients with systemic lupus erythematosus. J Clin Invest 1994;94:345.

    PubMed  CAS  Google Scholar 

  51. Zhou T, Bluethmann H, Zhang J, Edwards CK II, Mountz JD: Defective maintenance of T cell tolerance to a superantigen in MRL-lpr/lpr mice. J Exp Med 1992;176:1063–1072.

    Article  PubMed  CAS  Google Scholar 

  52. Scott DE, Kisch WJ, Steinberg AD: Studies of T cell deletion and T cell anergy following in vivo administration of SEB to normal and lupus-prone mice. J Immunol 1993; 150:664–672.

    PubMed  CAS  Google Scholar 

  53. Herron LR, Eisenberg RA, Roper E, Kakkanaiah VN, Cohen PL, Kotzin BL: Selection of the T cell receptor repertoire inlpr mice. J Immunol 1993;151:3450–3459.

    PubMed  CAS  Google Scholar 

  54. Berg LJ, Fazekas de St. Groth B, Groth BF, Pullen AM, Davis MM: Phenotypic differences between αΒ versus Β T-cell receptor transgenic mice undergoing negative selection. Nature 1989;340:559–562.

    Article  PubMed  CAS  Google Scholar 

  55. Bill J, Kanagawa O, Linten J, Utsunomiya Y, Palmer E: Class I and class II MHC gene products differentially affect the fate of Vb5 bearing thymocytes. J Mol Cell Immunol 1990;4:269–279.

    PubMed  CAS  Google Scholar 

  56. Fink PJ, Swan K, Turk G, Moore MW, Carbone FR: Both intrathymic and peripheral selection modulate the differential expression of VΒ5 among CD4+ and CD8+ T cells. J Exp Med 1992; 176:1733–1738.

    Article  PubMed  CAS  Google Scholar 

  57. Kisielow P, Bluthmann H, Staerz UD, Steinmetz M, von Boehmer H: Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes. Nature 1988;333:742–746.

    Article  PubMed  CAS  Google Scholar 

  58. Sha WC, Nelson CA, Newberry RD, Kranz DM, Russell JH, Loh DY: Positive and negative selection of an antigen receptor on T cells in transgenic mice. Nature 1988;336:73–76.

    Article  PubMed  CAS  Google Scholar 

  59. Smyth L, Howell M, Crispe IN: Self-reactivity and the expression of memory markers vary independently in MRL-Mp+/+ and MRL-Mp-lpr/lpr mice. Dev Immunol 1992;2:309–318.

    PubMed  CAS  Google Scholar 

  60. Castro JE, Listman JA, Jacobson BA, Wang Y, Lopez PA, Ju S, et al.: Fas modulation of apoptosis during negative selection of thymocytes. Immunity 1996;5: 617–627.

    Article  PubMed  CAS  Google Scholar 

  61. Sytwu HK, Liblau RS, McDevitt HO:The roles of Fas/APO-1 (CD95) and TNF in antigen-induced programmed cell death in T cell receptor transgenic mice. Immunity 1996;5:17–30.

    Article  PubMed  CAS  Google Scholar 

  62. Singer GG, Abbas AK: The Fas antigen is involved in peripheral but not thymic deletion of T lymphocytes in T cell receptor transgenic mice. Immunity 1994;1: 365–371.

    Article  PubMed  CAS  Google Scholar 

  63. Fatenejad S, Peng S, Disorbo O, Craft J: Central T cell tolerance in lupus-prone mice: Influence of autoimmune background and thelpr mutation. J Immunol 1998; 161:6427–6432.

    PubMed  CAS  Google Scholar 

  64. Kretz-Rommel A, Duncan SR, Rubin RL: Autoimmunity caused by disruption of central T cell tolerance: A murine model of drug-induced lupus. J Clin Invest 1997;99:1888–1896.

    PubMed  CAS  Google Scholar 

  65. Peng S, Cappadona J, McNiff J, Madaio M, Owen M, Hayday A, et al.: Pathogenesis of autoimmunity in αΒ T cell-deficient lupus-prone mice. Clin Exp Immunol 1998; 111:107–116.

    Article  PubMed  CAS  Google Scholar 

  66. Peng SL, McNiff JM, Madaio MP, Ma J, Owen M, Flavell RA, et al.: αΒ T cell regulation and CD40 ligand dependence in murine systemic autoimmunity. J Immunol 1997;158:2464–2470.

    PubMed  CAS  Google Scholar 

  67. Ferrick DA, Schrenzel MD, Mulvania T, Hsieh B, Ferlin WG, Lepper H: Differential production of interferon-γ and interleukin-4 in response to Th1- and Th2-stimulating pathogens by γδ T cellsin vivo. Nature 1995; 373:255–257.

    Article  PubMed  CAS  Google Scholar 

  68. Fujihashi K, Taguchi T, Aicher WK: Immunoregulatory functions for murine intraepithelial lymphocytes: γ/δ T cell receptor-positive (TCR+) T cells abrogate oral tolerance, while α/Β TCR+ T cells provide B cell help. J Exp Med 1992; 175:695–707.

    Article  PubMed  CAS  Google Scholar 

  69. van Vlasselaer P, Gascan H, de Waal Malefyt R, de Vries JE: IL-2 and a contact-mediated signal provided by TCRαΒ+ or TCRγδ+ CD4+ T cells induce polyclonal Ig production by committed human B cells. Enhancement by IL-5, specific inhibition of IgA synthesis by IL-4. J Immunol 1992; 148:1674–1684.

    PubMed  Google Scholar 

  70. McMenamin C, Pimm C, McKersey M, Holt PG: Regulation of IgE responses to inhaled antigen in mice by antigen-specific γδ T cells. Science 1994;265: 1869–1871.

    Article  PubMed  CAS  Google Scholar 

  71. Wen L, Roberts SJ, Viney JL, Wong FS, Mallick C, Findly RC, et al.: Immunoglobulin synthesis and generalized autoimmunity in mice congenitally deficient in αΒ(+) T cells. Nature 1994;369: 654–658.

    Article  PubMed  CAS  Google Scholar 

  72. Horner AA, Jabara H, Ramesh N, Geha RS: γ/δ T lymphocytes express CD40 ligand and induce isotype switching in B lymphocytes. J Exp Med 1995;181:1239–1244.

    Article  PubMed  CAS  Google Scholar 

  73. Peterman GM, Spencer C, Sperling AI, Bluestone JA: Role of γδ T cells in murine collagen-induced arthritis. J Immunol 1993; 151: 6546–6558.

    PubMed  CAS  Google Scholar 

  74. Maeda T, Saikawa I, Hotokebuchi T, Sugioka Y, Eto M, Murakami Y, et al.: Exacerbation of established collagen-induced arthritis in mice treated with an anti-T cell receptor antibody. Arthritis Rheum 1994;37:406–413.

    Article  PubMed  CAS  Google Scholar 

  75. Pelegrí C, Kühnlein P, Buchner E, Schmidt CB, Franch A, Castell M, et al.: Depletion of γ/δ T cells does not prevent or ameliorate, but rather aggravates, rat adjuvant arthritis. Arthritis Rheum 1996;39: 204–215.

    Article  PubMed  Google Scholar 

  76. Thurau SR, Kühnlein P, Hünig T, Wildner G: The role of gamma-delta T cells in induction and suppression of autoimmune uveitis [Abstract], Immunobiology 1995; 194:157.

    Google Scholar 

  77. Rajagopalan S, Zordan T, Tsokos GC, Datta SK Pathogenic anti-DNA autoantibody-inducing T helper cell lines from patients with active lupus nephritis: isolation of CD4-8- T helper cell lines that express the γδ T-cell antigen receptor. PNAS 1990;87:7020–7024.

    Article  PubMed  CAS  Google Scholar 

  78. Dianda L, Gulbranson-Judge A, Pao W, Hayday AC, MacLennan ICM, Owen MJ: Germinal center formation in mice lacking αΒ T cells. Eur J Immunol 1996;26: 1603–1607.

    Article  PubMed  CAS  Google Scholar 

  79. Peng SL, Madaio MP, Hayday AC, Craft J: Propagation and regulation of systemic autoimmunity by γδ T cells. J Immunol 1996; 157:5689–5698.

    PubMed  CAS  Google Scholar 

  80. Mizoguchi A, Mizoguchi E, Chiba C, Spiekermann GM, Tonegawa S, Nagler-Anderson C, et al.: Cytokine imbalance and autoantibody production in T cell receptor-α mutant mice with inflammatory bowel disease. J Exp Med 1996; 183:847–856.

    Article  PubMed  CAS  Google Scholar 

  81. Eichelberger M, McMickle A, Blackman M, Mombaerts P, Tonegawa S, Doherty PC: Functional analysis of the TCRα-Β+ cells that accumulate in the pneumonic lung of influenza virus-infected TCR-α-/- mice. J Immunol 1995; 154:1569–1576.

    PubMed  CAS  Google Scholar 

  82. Klinman DM, Steinberg AD: Systemic autoimmune disease arises from polyclonal B cell activation. J Exp Med 1987;165:1755–1760.

    Article  PubMed  CAS  Google Scholar 

  83. Abed NS, Chace JH, Cowdery JS: T cell-independent and T cell-dependent B cell activation increases IFN-γR expression and renders B cells sensitive to IFN-g-mediated inhibition. J Immunol 1994;153: 3369–3377.

    PubMed  CAS  Google Scholar 

  84. Rathmell JC, Cooke MP, Ho WY, Grein J, Townsend SE, Davis MM, et al.: CD95 (Fas)-dependent elimination of self-reactive B cells upon interaction with CD4+ Tcells. Nature 1995;376:181–184.

    Article  PubMed  CAS  Google Scholar 

  85. Chan O, Shlomchik MJ: A new role of B cells in systemic autoimmunity: B cells promote spontaneous T cell activation in MRL-lpr/lpr mice. J Immunol 1998; 160:51–59.

    PubMed  CAS  Google Scholar 

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  1. Section of Rheumatology, Department of Medicine, Yale University School of Medicine, 333 Cedar Street, 06520-8031, New Haven, CT

    Joe Craft, Stanford Peng, Takao Fujii, Masato Okada & Saeed Fatenejad

  2. Department of Biology, Yale University, 06520, New Haven, CT

    Stanford Peng

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  1. Joe Craft
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Craft, J., Peng, S., Fujii, T. et al. Autoreactive T cells in murine lupus. Immunol Res 19, 245–257 (1999). https://doi.org/10.1007/BF02786492

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