Advertisement

Inflammation

, Volume 31, Issue 6, pp 372–383 | Cite as

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

  • C. Schaufelberger
  • R. Andersson
  • E. Nordborg
  • G. K. Hansson
  • C. Nordborg
  • J. Wahlström
Article

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.

KEY WORDS

T cell T cell receptor V gene segment giant cell arteritis temporal artery 

Notes

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.

References

  1. 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.PubMedCrossRefGoogle Scholar
  2. 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.PubMedCrossRefGoogle Scholar
  3. 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.PubMedGoogle Scholar
  4. 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.PubMedCrossRefGoogle Scholar
  5. 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.PubMedCrossRefGoogle Scholar
  6. 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.PubMedCrossRefGoogle Scholar
  7. 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.PubMedGoogle Scholar
  8. 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.PubMedGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. 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.PubMedGoogle Scholar
  12. 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.PubMedCrossRefGoogle Scholar
  13. 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.CrossRefGoogle Scholar
  14. 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.PubMedGoogle Scholar
  15. 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.PubMedGoogle Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. 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.PubMedCrossRefGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. 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.PubMedCrossRefGoogle Scholar
  22. 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.PubMedCrossRefGoogle Scholar
  23. 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.PubMedGoogle Scholar
  24. 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.PubMedCrossRefGoogle Scholar
  25. 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.PubMedCrossRefGoogle Scholar
  26. 26.
    Grunewald, J., and H. Wigzell. 1996. T-cell expansions in healthy individuals. Immunologist. 4:99–103.Google Scholar
  27. 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.PubMedCrossRefGoogle Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. 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.PubMedGoogle Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. 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.PubMedCrossRefGoogle Scholar
  33. 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.PubMedCrossRefGoogle Scholar
  34. 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.PubMedGoogle Scholar
  35. 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.PubMedCrossRefGoogle Scholar
  36. 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.PubMedCrossRefGoogle Scholar
  37. 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.PubMedCrossRefGoogle Scholar
  38. 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.PubMedCrossRefGoogle Scholar
  39. 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.PubMedCrossRefGoogle Scholar
  40. 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.PubMedCrossRefGoogle Scholar
  41. 41.
    Levine, S. M., and D. B. Hellmann. 2002. Giant cell arteritis. Curr. Opin. Rheumatol. 14:3–10. doi: 10.1097/00002281-200201000-00002.PubMedCrossRefGoogle Scholar
  42. 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.PubMedCrossRefGoogle Scholar
  43. 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.PubMedCrossRefGoogle Scholar
  44. 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.PubMedCrossRefGoogle Scholar
  45. 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.PubMedCrossRefGoogle Scholar
  46. 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.PubMedCrossRefGoogle Scholar
  47. 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.PubMedGoogle Scholar
  48. 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.PubMedCrossRefGoogle Scholar
  49. 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.PubMedGoogle Scholar
  50. 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.PubMedGoogle Scholar
  51. 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.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • C. Schaufelberger
    • 1
  • R. Andersson
    • 2
    • 5
  • E. Nordborg
    • 1
  • G. K. Hansson
    • 3
  • C. Nordborg
    • 4
  • J. Wahlström
    • 3
  1. 1.Department of RheumatologySahlgrenska University HospitalGöteborgSweden
  2. 2.Department of Infectious DiseasesSahlgrenska University HospitalGöteborgSweden
  3. 3.Department of Medicine, Solna, Karolinska InstitutetKarolinska University Hospital L4:01StockholmSweden
  4. 4.Department of PathologySahlgrenska University HospitalGöteborgSweden
  5. 5.Research and Development CentreSkaraborg HospitalSkövdeSweden

Personalised recommendations