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Wie werden T-Zellen im Gelenk aktiviert?

How do T-cells become activated in joints?

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Zeitschrift für Rheumatologie Aims and scope Submit manuscript

Zusammenfassung

CD4-positive T-Zellen sind bei der rheumatoiden Arthritis (RA) pathologisch aktiviert und in die gelenkdestruierende Autoimmunantwort involviert. Neben ihrer proinflammatorischen Zytokinproduktion spielt insbesondere ihre Unterstützung der autoreaktiven „B-Zell-Response“ (die so genannte T-Zell-Hilfe für B-Zellen) eine Rolle. Ihre vermutlich wichtigste Rolle dürfte jedoch die Erkennung von Autoantigenen als entscheidendem Schritt in der Pathogenese der RA sein. Die selektive Hemmung dieses Prozesses bleibt weiterhin eines der spannendsten therapeutischen Ziele für die Zukunft.

Abstract

Activated CD4+ T-cells are found in joints of patients with rheumatoid arthritis and are involved in the joint destroying autoimmune response. Besides proinflammatory cytokine production T-cells are indispensable for the activation of B-cells, the so-called T-cell help for B-cells. However, the recognition of autoantigens by T-cells seems of utmost importance for the pathogenesis of rheumatoid arthritis. Selective inhibition of this process is therefore one of the most interesting therapeutic targets for the future.

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Literatur

  1. Auger I, Sebbag M, Vincent C et al (2005) Influence of HLA-DR genes on the production of rheumatoid arthritis-specific autoantibodies to citrullinated fibrinogen. Arthritis Rheum 52:3424–3432

    Article  CAS  PubMed  Google Scholar 

  2. Bettelli E, Carrier Y, Gao W et al (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441:235–238

    Article  CAS  PubMed  Google Scholar 

  3. Buch MH, Boyle DL, Rosengren S et al (2009) Mode of action of abatacept in rheumatoid arthritis patients having failed tumour necrosis factor blockade: a histological, gene expression and dynamic magnetic resonance imaging pilot study. Ann Rheum Dis 68:1220–1227

    Article  CAS  PubMed  Google Scholar 

  4. Hill JA, Southwood S, Sette A et al (2003) Cutting edge: the conversion of arginine to citrulline allows for a high-affinity peptide interaction with the rheumatoid arthritis-associated HLA-DRB1*0401 MHC class II molecule. J Immunol 171:538–541

    CAS  PubMed  Google Scholar 

  5. Hill JA, Bell DA, Brintnell W et al (2008) Arthritis induced by posttranslationally modified (citrullinated) fibrinogen in DR4-IE transgenic mice. J Exp Med 205:967–979

    Article  CAS  PubMed  Google Scholar 

  6. Huizinga TW, Amos CI, Helm-van Mil AH van der et al (2005) Refining the complex rheumatoid arthritis phenotype based on specificity of the HLA-DRB1 shared epitope for antibodies to citrullinated proteins. Arthritis Rheum 52:3433–3438

    Article  CAS  PubMed  Google Scholar 

  7. Kaltenhäuser S, Pierer M, Arnold S et al (2007) Antibodies against cyclic citrullinated peptide are associated with the DRB1 shared epitope and predict joint erosion in rheumatoid arthritis. Rheumatology (Oxford) 46:100–104

    Google Scholar 

  8. Kojima M, Motoori T, Nakamura S (2006) Benign, atypical and malignant lymphoproliferative disorders in rheumatoid arthritis patients. Biomed Pharmacother 60:663–672

    Article  CAS  PubMed  Google Scholar 

  9. Langrish CL, Chen Y, Blumenschein WM et al (2005) IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201:233–240

    Article  CAS  PubMed  Google Scholar 

  10. Lefèvre S, Knedla A, Tennie C et al (2009) Synovial fibroblasts spread rheumatoid arthritis to unaffected joints. Nat Med 15:1414–1420

    Article  PubMed  Google Scholar 

  11. Lin SC, Yen JH, Tsai JJ et al (2004) Association of a programmed death 1 gene polymorphism with the development of rheumatoid arthritis, but not systemic lupus erythematosus. Arthritis Rheum 50:770–775

    Article  CAS  PubMed  Google Scholar 

  12. Mandik-Nayak L, Wipke BT, Shih FF et al (2002) Despite ubiquitous autoantigen expression, arthritogenic autoantibody response initiates in the local lymph node. Proc Natl Acad Sci U S A 99:14368–14373

    Article  CAS  PubMed  Google Scholar 

  13. Mangan PR, Harrington LE, O‘ Quinn DB et al (2006) Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 441:231–234

    Article  CAS  PubMed  Google Scholar 

  14. Martens PB, Goronzy JJ, Schaid D, Weyand CM (1997) Expansion of unusual CD4+ T cells in severe rheumatoid arthritis. Arthritis Rheum 40:1106–1114

    Article  CAS  PubMed  Google Scholar 

  15. McInnes IB, Leung BP, Sturrock RD et al (1997) Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-alpha production in rheumatoid arthritis. Nat Med 3:189–195

    Article  CAS  PubMed  Google Scholar 

  16. McInnes IB, Schett G (2007) Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 7:429–442

    Article  CAS  PubMed  Google Scholar 

  17. Motulsky AG, Weinberg S, Saphir O, Rosenberg E (1952) Lymph nodes in rheumatoid arthritis. AMA Arch Intern Med 90:660–676

    CAS  PubMed  Google Scholar 

  18. Namekawa T, Snyder MR, Yen JH et al (2000) Killer cell activating receptors function as costimulatory molecules on CD4+CD28null T cells clonally expanded in rheumatoid arthritis. J Immunol 165:1138–1145

    CAS  PubMed  Google Scholar 

  19. Niesner U, Albrecht I, Janke M et al (2008) Autoregulation of Th1-mediated inflammation by twist1. J Exp Med 205:1889–1901

    Article  CAS  PubMed  Google Scholar 

  20. Nosanchuk JS, Schnitzer B (1969) Follicular hyperplasia in lymph nodes from patients with rheumatoid arthritis. A clinicopathologic study. Cancer 24:243–254

    Article  CAS  PubMed  Google Scholar 

  21. Olszewski WL, Pazdur J, Kubasiewicz E et al (2001) Lymph draining from foot joints in rheumatoid arthritis provides insight into local cytokine and chemokine production and transport to lymph nodes. Arthritis Rheum 44:541–549

    Article  CAS  PubMed  Google Scholar 

  22. Plenge RM, Padyukov L, Remmers EF et al (2005) Replication of putative candidate-gene associations with rheumatoid arthritis in >4,000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4 and PADI4. Am J Hum Genet 77:1044–1060

    Article  CAS  PubMed  Google Scholar 

  23. Prots I, Skapenko A, Wendler J et al (2006) Association of the IL4R single-nucleotide polymorphism I50 V with rapidly erosive rheumatoid arthritis. Arthritis Rheum 54:1491–1500

    Article  CAS  PubMed  Google Scholar 

  24. Raychaudhuri S, Remmers EF, Lee AT et al (2008) Common variants at CD40 and other loci confer risk of rheumatoid arthritis. Nat Genet 40:1216–1223

    Article  CAS  PubMed  Google Scholar 

  25. Remmers EF, Plenge RM, Lee AT et al (2007) STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med 357:977–986

    Article  CAS  PubMed  Google Scholar 

  26. Snyder MR, Nakajima T, Leibson PJ et al (2004) Stimulatory killer Ig-like receptors modulate T cell activation through DAP12-dependent and DAP12-independent mechanisms. J Immunol 173:3725–3731

    CAS  PubMed  Google Scholar 

  27. Swanberg M, Lidman O, Padyukov L et al (2005) MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction. Nat Genet 37:486–494

    Article  CAS  PubMed  Google Scholar 

  28. Taneja V, David CS (2010) Role of HLA class II genes in susceptibility/resistance to inflammatory arthritis: studies with humanized mice. Immunol Rev 233:62–78

    Article  CAS  PubMed  Google Scholar 

  29. Vanden Eijnden S, Goriely S, De Wit D et al (2005) IL-23 up-regulates IL-10 and induces IL-17 synthesis by polyclonally activated naive T cells in human. Eur J Immunol 35:469–475

    Article  Google Scholar 

  30. Vang T, Congia M, Macis MD et al (2005) Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat Genet 37:1317–1319

    Article  CAS  PubMed  Google Scholar 

  31. Veldhoen M, Hocking RJ, Atkins CJ et al (2006) TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24:179–189

    Article  CAS  PubMed  Google Scholar 

  32. Wagner UG, Kurtin PJ, Wahner A et al (1998) The role of CD8+ CD40L+ T cells in the formation of germinal centers in rheumatoid synovitis. J Immunol 161:6390–6397

    CAS  PubMed  Google Scholar 

  33. Wagner U, Pierer M, Kaltenhäuser S et al (2003) Clonally expanded CD4+CD28null T cells in rheumatoid arthritis use distinct combinations of T cell receptor BV and BJ elements. Eur J Immunol 33:79–84

    Article  CAS  PubMed  Google Scholar 

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  1. Sektion Rheumatologie, Medizinische Klinik II, Universität Leipzig, Liebigstr. 20, 04103, Leipzig, Deutschland

    M. Pierer & U. Wagner

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  1. M. Pierer
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  2. U. Wagner
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Correspondence to M. Pierer.

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Pierer, M., Wagner, U. Wie werden T-Zellen im Gelenk aktiviert?. Z. Rheumatol. 69, 738–742 (2010). https://doi.org/10.1007/s00393-010-0698-x

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