RECOGNITION OF TISSUE RESIDING ANTIGEN BY T-CELLS IN VASCULITIC LESIONS OF GIANT-CELL ARTERITIS

The objective of this study was to explore the nature of the antigen-s pecific T cell response in giant cell arteritis by analyzing clonally expanded T cells in temporal artery specimens. In temporal artery tiss ue from eight patients, 10% of the T cell receptor beta chain repertoi re was systematically screened for clonal T cells by reverse-transcrip tase polymerase chain reaction with selected BV, BJ, and BC specific p rimers and by direct sequencing of the amplified product. In five addi tional patients tissue-derived T cell clones were characterized. All e xpanded clonotypes were analyzed for their presence at different sites of the inflamed artery. T cell lines were tested for their proliferat ion to autologous monocytes pulsed with temporal artery extracts from patients with giant cell arteritis, polymyalgia rheumatica, and unrela ted 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 th e peripheral blood. The T cell receptor beta chain sequences were dive rse. The patients had between none and five such clonotypes in the sam pled repertoire, suggesting that only few T cell specificities in each patient are involved in antigen recognition. One of these T cell clon otypes was shown to proliferate in response to an antigen selectively expressed in temporal artery specimens from giant cell arteritis and f rom polymyalgia rheumatica patients. Clonotypes with identical T cell receptor beta chain sequences can be found at distinct sites of the in flammation in giant cell arteritis, suggesting recognition of the same antigen at different locations. At least for some of these T cell clo nes the antigen is shared between different giant cell arteritis and p olymyalgia rheumatica patients but not expressed in temporal arteries of patients with unrelated diseases. While different HLA-DR4(+) patien ts utilize distinct T cell specificities, the actual number of respond ing T cells in individual patients is small and may be disease limitin g.