Recognition of tissue residing antigen by T cells in vasculitic lesions of dent cell arteritis

V. Martinez-Taboada, N. N.H. Hunder, G. G. Hunder, C. M. Weyand, J. J. Goronzy

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

The objective of this study was to explore the nature of the antigen-specific T cell response in giant cell arteritis by analyzing clonally expanded T cells in temporal artery specimens. In temporal artery tissue from eight patients, 10% of the T cell receptor β chain repertoire was systematically screened for clonal T cells by reverse-transcriptase polymerase chain reaction with selected BV, BJ, and BC specific primers and by direct sequencing of the amplified product. In vivo additional patients tissue-derived T cell clones were characterized. All expanded clonotypes were analyzed for their presence at different sites of the inflamed artery. T cell lines were tested for their proliferation to autologous monocytes pulsed with temporal artery extracts from patients with giant cell arteritis, polymyalgia rheumatica, and unrelated diseases. Clonally expanded T cells were identified in 30% of the BV-J combinations of the sampled repertoire. A subset of these clones were encountered at different sites of the inflammation, but not in the peripheral blood. The T cell receptor β chain sequences were diverse. The patients had between none and five such clonotypes in the sampled repertoire, suggesting that only few T cell specificities in each patient are involved in antigen recognition. One of these T cell clonotypes was shown to proliferate in response to an antigen selectively expressed in temporal artery specimens from giant cell arteritis and from polymyalgia rheumatica patients. Clonotypes with identical T cell receptor β chain sequences can be found at distinct sites of the inflammation in giant cell arteritis, suggesting recognition of the same antigen at different locations. At least for some of these T cell clones the antigen is shared between different giant cell arteritis and polymyalgia rheumatica patients but not expressed in temporal arteries of patients with unrelated diseases. While different HLA-DR4+ patients utilize distinct T cell specificities, the actual number of responding T cells in individual patients is small and may be disease limiting.

Original languageEnglish (US)
Pages (from-to)695-703
Number of pages9
JournalJournal of Molecular Medicine
Volume74
Issue number11
DOIs
StatePublished - 1996

Keywords

  • Autoimmunity
  • Giant cell arteritis
  • T cell receptor
  • Vasculitis

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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