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An Uneven Expression of T Cell Receptor V Genes in the Arterial Wall and Peripheral Blood in Giant Cell Arteritis

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Abstract

The aim of the study was to investigate T cell receptor (TCR) usage at the time of diagnosis of giant cell arteritis (GCA) and to estimate the degree of clonality of T-cells infiltrating the lesion. Seven patients with biopsy-proven giant cell arteritis were included in the study. Immunocytochemistry in biopsies from the temporal arteries and flow cytometric analysis of peripheral blood lymphocytes (PBL) was performed using monoclonal antibodies specific for CD3, CD4 and CD8 and 13 TCR Vα and Vβ gene segment products. The CDR3 fragment length polymorphism was assessed by gel electrophoresis of PCR-amplified TCR segments. The T lymphocytes were found to be concentrated to the adventitia rather than the media or intima. Six of the seven patients with GCA had expansions of T lymphocytes, expressing selected TCR V genes in the arterial wall. None of these expansions was found in PBL. The infiltrating T-cells were poly- or oligoclonal. In conclusion, the dominating part of the inflammatory infiltrate in GCA emanates from the adventitial microvessels. There is an uneven expression of TCR V genes by T lymphocytes in the inflammatory infiltrates as compared to peripheral blood T lymphocytes at the time of diagnosis, consistent with an antigen-driven immunological reaction in the arterial wall.

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References

  1. Weyand, C. M., and J. J. Goronzy. 2003. Medium- and large-vessel vasculitis. N. Engl. J. Med. 349:160–169. doi:10.1056/NEJMra022694.

    Article  PubMed  CAS  Google Scholar 

  2. Schaufelberger, C., B. A. Bengtsson, and R. Andersson. 1995. Epidemiology and mortality in 220 patients with polymyalgia rheumatica. Br. J. Rheumatol. 34:261–264. doi:10.1093/rheumatology/34.3.261.

    Article  PubMed  CAS  Google Scholar 

  3. Nordborg, E., B. A. Bengtsson, V. Petursdottir, and C. Nordborg. 1997. Morphological aspects of giant cells in giant cell arteritis: an electron-microscopic and immunocytochemical study. Clin. Exp. Rheumatol. 15:129–134.

    PubMed  CAS  Google Scholar 

  4. Weyand, C. M., K. C. Hicok, G. G. Hunder, and J. J. Goronzy. 1992. The HLA-DRB1 locus as a genetic component in giant cell arteritis. Mapping of a disease-linked sequence motif to the antigen binding site of the HLA-DR molecule. J. Clin. Invest. 90:2355–2361. doi:10.1172/JCI116125.

    Article  PubMed  CAS  Google Scholar 

  5. Weyand, C. M., W. Ma-Krupa, and J. J. Goronzy. 2004. Immunopathways in giant cell arteritis and polymyalgia rheumatica. Autoimmun. Rev. 3:46–53. doi:10.1016/S1568-9972(03)00064-8.

    Article  PubMed  Google Scholar 

  6. Banks, P. M., M. D. Cohen, W. W. Ginsburg, and G. G. Hunder. 1983. Immunohistologic and cytochemical studies of temporal arteritis. Arthritis Rheum. 26:1201–1207doi:10.1002/art.1780261005.

    Article  PubMed  CAS  Google Scholar 

  7. Andersson, R., G. K. Hansson, T. Soderstrom, R. Jonsson, B. A. Bengtsson, and E. Nordborg. 1988. HLA-DR expression in the vascular lesion and circulating T lymphocytes of patients with giant cell arteritis. Clin. Exp. Immunol. 73:82–87.

    PubMed  CAS  Google Scholar 

  8. Cid, M. C., E. Campo, G. Ercilla, A. Palacin, J. Vilaseca, J. Villalta, and M. Ingelmo. 1989. Immunohistochemical analysis of lymphoid and macrophage cell subsets and their immunologic activation markers in temporal arteritis. Influence of corticosteroid treatment. Arthritis Rheum. 32:884–893.

    PubMed  CAS  Google Scholar 

  9. Schaufelberger, C., S. Stemme, R. Andersson, and G. K. Hansson. 1993. T lymphocytes in giant cell arteritic lesions are polyclonal cells expressing alpha beta type antigen receptors and VLA-1 integrin receptors. Clin. Exp. Immunol. 91:421–428.

    Article  PubMed  CAS  Google Scholar 

  10. Andersson, R., R. Jonsson, A. Tarkowski, B. A. Bengtsson, and B. E. Malmvall. 1987. T cell subsets and expression of immunological activation markers in the arterial walls of patients with giant cell arteritis. Ann. Rheum. Dis. 46:915–923. doi:10.1136/ard.46.12.915.

    Article  PubMed  CAS  Google Scholar 

  11. Weyand, C. M., K. C. Hicok, G. G. Hunder, and J. J. Goronzy. 1994. Tissue cytokine patterns in patients with polymyalgia rheumatica and giant cell arteritis. Ann. Intern. Med. 121:484–491.

    PubMed  CAS  Google Scholar 

  12. Weyand, C. M., N. Tetzlaff, J. Bjornsson, A. Brack, B. Younge, and J. J. Goronzy. 1997. Disease patterns and tissue cytokine profiles in giant cell arteritis. Arthritis Rheum. 40:19–26. doi:10.1002/art.1780400105.

    Article  PubMed  CAS  Google Scholar 

  13. Bruhl, H., V. Vielhauer, M. Weiss, M. Mack, D. Schlondorff, and S. Segerer. 2005. Expression of DARC, CXCR3 and CCR5 in giant cell arteritis. Rheumatology (Oxford) 44:309–313. doi:10.1093/rheumatology/keh485.

    Article  CAS  Google Scholar 

  14. Brack, A., A. Geisler, V. M. Martinez-Taboada, B. R. Younge, J. J. Goronzy, and C. M. Weyand. 1997. Giant cell vasculitis is a T cell-dependent disease. Mol. Med. 3:530–543.

    PubMed  CAS  Google Scholar 

  15. Kaiser, M., B. Younge, J. Bjornsson, J. J. Goronzy, and C. M. Weyand. 1999. Formation of new vasa vasorum in vasculitis. Production of angiogenic cytokines by multinucleated giant cells. Am. J. Pathol. 155:765–774.

    PubMed  CAS  Google Scholar 

  16. Kaiser, M., C. M. Weyand, J. Bjornsson, and J. J. Goronzy. 1998. Platelet-derived growth factor, intimal hyperplasia, and ischemic complications in giant cell arteritis. Arthritis Rheum. 41:623–633. doi:10.1002/1529-0131(199804)41:4<623::AID-ART9>3.0.CO;2-6.

    Article  PubMed  CAS  Google Scholar 

  17. Moss, P. A., W. M. Rosenberg, and J. I. Bell. 1992. The human T cell receptor in health and disease. Annu. Rev. Immunol. 10:71–96. doi:10.1146/annurev.iy.10.040192.000443.

    Article  PubMed  CAS  Google Scholar 

  18. Davis, M. M., and P. J. Bjorkman. 1988. T-cell antigen receptor genes and T-cell recognition. Nature. 334:395–402. doi:10.1038/334395a0.

    Article  PubMed  CAS  Google Scholar 

  19. Grunewald, J., R. Andersson, L. Rydberg, D. Gigliotti, C. Schaufelberger, G. K. Hansson, and H. Wigzell. 1994. CD4+ and CD8+ T cell expansions using selected TCR V and J gene segments at the onset of giant cell arteritis. Arthritis Rheum. 37:1221–1227. doi:10.1002/art.1780370817.

    Article  PubMed  CAS  Google Scholar 

  20. Martinez-Taboada, V. M., J. J. Goronzy, and C. M. Weyand. 1996. Clonally expanded CD8 T cells in patients with polymyalgia rheumatica and giant cell arteritis. Clin. Immunol. Immunopathol. 79:263–270. doi:10.1006/clin.1996.0078.

    Article  PubMed  CAS  Google Scholar 

  21. Weyand, C. M., J. Schonberger, U. Oppitz, N. N. Hunder, K. C. Hicok, and J. J. Goronzy. 1994. Distinct vascular lesions in giant cell arteritis share identical T cell clonotypes. J. Exp. Med. 179:951–960. doi:10.1084/jem.179.3.951.

    Article  PubMed  CAS  Google Scholar 

  22. Martinez-Taboada, V., N. N. Hunder, G. G. Hunder, C. M. Weyand, and J. J. Goronzy. 1996. Recognition of tissue residing antigen by T cells in vasculitic lesions of giant cell arteritis. J. Mol. Med. 74:695–703. doi:10.1007/s001090050074.

    Article  PubMed  CAS  Google Scholar 

  23. Hunder, G. G., D. A. Bloch, B. A. Michel, M. B. Stevens, W. P. Arend, L. H. Calabrese, S. M. Edworthy, A. S. Fauci, R. Y. Leavitt, J. T. Lie, et al. 1990. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum. 33:1122–1128.

    PubMed  CAS  Google Scholar 

  24. Grunewald, J., O. Olerup, U. Persson, M. B. Ohrn, H. Wigzell, and A. Eklund. 1994. T-cell receptor variable region gene usage by CD4+ and CD8+ T cells in bronchoalveolar lavage fluid and peripheral blood of sarcoidosis patients. Proc. Natl. Acad. Sci. U.S.A. 91:4965–4969. doi:10.1073/pnas.91.11.4965.

    Article  PubMed  CAS  Google Scholar 

  25. Halapi, E., A. Werner, J. Wahlstrom, A. Osterborg, M. Jeddi-Tehrani, Q. Yi, C. H. Janson, H. Wigzell, J. Grunewald, and H. Mellstedt. 1997. T cell repertoire in patients with multiple myeloma and monoclonal gammopathy of undetermined significance: clonal CD8+ T cell expansions are found preferentially in patients with a low tumor burden. Eur. J. Immunol. 27:2245–2252. doi:10.1002/eji.1830270919.

    Article  PubMed  CAS  Google Scholar 

  26. Grunewald, J., and H. Wigzell. 1996. T-cell expansions in healthy individuals. Immunologist. 4:99–103.

    CAS  Google Scholar 

  27. Choi, Y. W., B. Kotzin, L. Herron, J. Callahan, P. Marrack, and J. Kappler. 1989. Interaction of Staphylococcus aureus toxin “superantigens” with human T cells. Proc. Natl. Acad. Sci. U.S.A. 86:8941–8945. doi:10.1073/pnas.86.22.8941.

    Article  PubMed  CAS  Google Scholar 

  28. Pannetier, C., M. Cochet, S. Darche, A. Casrouge, M. Zoller, and P. Kourilsky. 1993. The sizes of the CDR3 hypervariable regions of the murine T-cell receptor beta chains vary as a function of the recombined germ-line segments. Proc. Natl. Acad. Sci. U.S.A. 90:4319–4323. doi:10.1073/pnas.90.9.4319.

    Article  PubMed  CAS  Google Scholar 

  29. Monteiro, J., R. Hingorani, I. H. Choi, J. Silver, R. Pergolizzi, and P. K. Gregersen. 1995. Oligoclonality in the human CD8+ T cell repertoire in normal subjects and monozygotic twins: implications for studies of infectious and autoimmune diseases. Mol. Med. 1:614–624.

    PubMed  CAS  Google Scholar 

  30. Wang, X. H., J. D. Ohmen, K. Uyemura, T. H. Rea, M. Kronenberg, and R. L. Modlin. 1993. Selection of T lymphocytes bearing limited T-cell receptor beta chains in the response to a human pathogen. Proc. Natl. Acad. Sci. U.S.A. 90:188–192. doi:10.1073/pnas.90.1.188.

    Article  PubMed  CAS  Google Scholar 

  31. Acha-Orbea, H. 1993. Bacterial and viral superantigens: roles in autoimmunity? Ann. Rheum. Dis. 52(Suppl 1):S6–16. doi:10.1136/ard.52.Suppl_1.S6.

    Article  PubMed  CAS  Google Scholar 

  32. Paliard, X., S. G. West, J. A. Lafferty, J. R. Clements, J. W. Kappler, P. Marrack, and B. L. Kotzin. 1991. Evidence for the effects of a superantigen in rheumatoid arthritis. Science. 253:325–329. doi:10.1126/science.1857971.

    Article  PubMed  CAS  Google Scholar 

  33. Zagon, G., J. R. Tumang, Y. Li, S. M. Friedman, and M. K. Crow. 1994. Increased frequency of V beta 17-positive T cells in patients with rheumatoid arthritis. Arthritis Rheum. 37:1431–1440. doi:10.1002/art.1780371005.

    Article  PubMed  CAS  Google Scholar 

  34. Giscombe, R., J. Grunewald, S. Nityanand, and A. K. Lefvert. 1995. T cell receptor (TCR) V gene usage in patients with systemic necrotizing vasculitis. Clin. Exp. Immunol. 101:213–219.

    PubMed  CAS  Google Scholar 

  35. Grunewald, J., R. Ahlberg, A. K. Lefvert, H. DerSimonian, H. Wigzell, and C. H. Janson. 1991. Abnormal T-cell expansion and V-gene usage in myasthenia gravis patients. Scand. J. Immunol. 34:161–168. doi:10.1111/j.1365-3083.1991.tb01533.x.

    Article  PubMed  CAS  Google Scholar 

  36. Abe, J., B. L. Kotzin, C. Meissner, M. E. Melish, M. Takahashi, D. Fulton, F. Romagne, B. Malissen, and D. Y. Leung. 1993. Characterization of T cell repertoire changes in acute Kawasaki disease. J. Exp. Med. 177:791–796. doi:10.1084/jem.177.3.791.

    Article  PubMed  CAS  Google Scholar 

  37. Sottini, A., L. Imberti, R. Gorla, R. Cattaneo, and D. Primi. 1991. Restricted expression of T cell receptor V beta but not V alpha genes in rheumatoid arthritis. Eur. J. Immunol. 21:461–466. doi:10.1002/eji.1830210231.

    Article  PubMed  CAS  Google Scholar 

  38. Gulwani-Akolkar, B., P. N. Akolkar, A. Minassian, R. Pergolizzi, M. McKinley, G. Mullin, S. Fisher, and J. Silver. 1996. Selective expansion of specific T cell receptors in the inflamed colon of Crohn's disease. J. Clin. Invest. 98:1344–1354. doi:10.1172/JCI118921.

    Article  PubMed  CAS  Google Scholar 

  39. Vanderlugt, C. J., and S. D. Miller. 1996. Epitope spreading. Curr. Opin. Immunol. 8:831–836. doi:10.1016/S0952-7915(96)80012-4.

    Article  PubMed  CAS  Google Scholar 

  40. Meinl, E., F. Weber, K. Drexler, C. Morelle, M. Ott, G. Saruhan-Direskeneli, N. Goebels, B. Ertl, G. Jechart, G. Giegerich, et al. 1993. Myelin basic protein-specific T lymphocyte repertoire in multiple sclerosis. Complexity of the response and dominance of nested epitopes due to recruitment of multiple T cell clones. J. Clin. Invest. 92:2633–2643. doi:10.1172/JCI116879.

    Article  PubMed  CAS  Google Scholar 

  41. Levine, S. M., and D. B. Hellmann. 2002. Giant cell arteritis. Curr. Opin. Rheumatol. 14:3–10. doi:10.1097/00002281-200201000-00002.

    Article  PubMed  Google Scholar 

  42. Dale, J. B., and E. H. Beachey. 1985. Epitopes of streptococcal M proteins shared with cardiac myosin. J. Exp. Med. 162:583–591. doi:10.1084/jem.162.2.583.

    Article  PubMed  CAS  Google Scholar 

  43. Kamradt, T., R. Goggel, and K. J. Erb. 2005. Induction, exacerbation and inhibition of allergic and autoimmune diseases by infection. Trends Immunol. 26:260–267. doi:10.1016/j.it.2005.03.009.

    Article  PubMed  CAS  Google Scholar 

  44. Halapi, E., M. Jeddi-Tehrani, A. Blucher, R. Andersson, P. Rossi, H. Wigzell, and J. Grunewald. 1999. Diverse T-cell receptor CDR3 length patterns in human CD4+ and CD8+ T lymphocytes from newborns and adults. Scand. J. Immunol. 49:149–154. doi:10.1046/j.1365-3083.1999.00469.x.

    Article  PubMed  CAS  Google Scholar 

  45. Lopez-Hoyos, M., M. J. Bartolome-Pacheco, R. Blanco, V. Rodriguez-Valverde, and V. M. Martinez-Taboada. 2004. Selective T cell receptor decrease in peripheral blood T lymphocytes of patients with polymyalgia rheumatica and giant cell arteritis. Ann. Rheum. Dis. 63:54–60. doi:10.1136/ard.2003.005900.

    Article  PubMed  CAS  Google Scholar 

  46. Mora, J. R., and U. H. von Andrian. 2006. T-cell homing specificity and plasticity: new concepts and future challenges. Trends Immunol. 27:235–243. doi:10.1016/j.it.2006.03.007.

    Article  PubMed  CAS  Google Scholar 

  47. Krupa, W. M., M. Dewan, M. S. Jeon, P. J. Kurtin, B. R. Younge, J. J. Goronzy, and C. M. Weyand. 2002. Trapping of misdirected dendritic cells in the granulomatous lesions of giant cell arteritis. Am. J. Pathol. 161:1815–1823.

    PubMed  CAS  Google Scholar 

  48. Ma-Krupa, W., M. S. Jeon, S. Spoerl, T. F. Tedder, J. J. Goronzy, and C. M. Weyand. 2004. Activation of arterial wall dendritic cells and breakdown of self-tolerance in giant cell arteritis. J. Exp. Med. 199:173–183. doi:10.1084/jem.20030850.

    Article  PubMed  CAS  Google Scholar 

  49. Wagner, A. D., U. Wittkop, A. Prahst, W. A. Schmidt, E. Gromnica-Ihle, K. Vorpahl, A. P. Hudson, and H. Zeidler. 2003. Dendritic cells co-localize with activated CD4+ T cells in giant cell arteritis. Clin. Exp. Rheumatol. 21:185–192.

    PubMed  CAS  Google Scholar 

  50. Wagner, A. D., J. Bjornsson, G. B. Bartley, J. J. Goronzy, and C. M. Weyand. 1996. Interferon-gamma-producing T cells in giant cell vasculitis represent a minority of tissue-infiltrating cells and are located distant from the site of pathology. Am. J. Pathol. 148:1925–1933.

    PubMed  CAS  Google Scholar 

  51. Weyand, C. M., A. D. Wagner, J. Bjornsson, and J. J. Goronzy. 1996. Correlation of the topographical arrangement and the functional pattern of tissue-infiltrating macrophages in giant cell arteritis. J. Clin. Invest. 98:1642–1649. doi:10.1172/JCI118959.

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank Margareta Persson, Fariba Moraghebi and Beata Faber for technical assistance. This study was supported by the Swedish Research Council, the Swedish Cancer Society, the Medical Society of Göteborg, the Swedish Heart-Lung Foundation, the Swedish Association against Rheumatism and the Amlöv Foundation.

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  1. R. Andersson

    Present address: Research and Development Centre, Skaraborg Hospital, 541 85, Skövde, Sweden

Authors and Affiliations

  1. Department of Rheumatology, Sahlgrenska University Hospital, 413 45, Göteborg, Sweden

    C. Schaufelberger & E. Nordborg

  2. Department of Infectious Diseases, Sahlgrenska University Hospital, 413 45, Göteborg, Sweden

    R. Andersson

  3. Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital L4:01, 171 76, Stockholm, Sweden

    G. K. Hansson & J. Wahlström

  4. Department of Pathology, Sahlgrenska University Hospital, 413 45, Göteborg, Sweden

    C. Nordborg

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  1. C. Schaufelberger
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Correspondence to J. Wahlström.

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Schaufelberger, C., Andersson, R., Nordborg, E. et al. An Uneven Expression of T Cell Receptor V Genes in the Arterial Wall and Peripheral Blood in Giant Cell Arteritis. Inflammation 31, 372–383 (2008). https://doi.org/10.1007/s10753-008-9088-9

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