INTERFERON-GAMMA-PRODUCING T-CELLS IN GIANT-CELL VASCULITIS REPRESENTA MINORITY OF TISSUE INFILTRATING CELLS AND ARE LOCATED DISTANT FROM THE SITE OF PATHOLOGY

Giant cell vasculitis is art arteritis that predominantly affects medi um- and large-sized arteries. Genetic risk factors and clonal expansio n of selected CD4(+) T cell specificities in the vascular lesions supp ort the model that giant cell arteritis is a T-cell-driven disease. In terferon (IFN)-gamma production in the tissue is intimately associated with the formation of the inflammatory infiltrates. Antigens inducing stimulation of T cells are unknown. To provide indirect evidence for the type and the tissue localization of the antigen, we examined CD4() T cells in the lesions that secrete IFN-gamma. Temporal artery speci mens from patients with giant cell arteritis were analyzed by two-colo r immunohistochemistry applying antibodies to T cell markers, IFN-gamm a, the interleukin-2 receptor alpha-chain (CD25) and talin, a cytoskel etal protein that is reorganized in T cells interacting with antigen-p resenting cells. Proliferating cells ira the lesions were identified t hrough the expression of the Ki-67 nuclear antigen. More than 90% of t issue-infiltrating, IFN-gamma-producing cells were CD4(+) CD45RO(+). T hey represented a minute subset (2 to 4%) of tissue-infiltrating T cel ls. IFN-gamma(+) T cells aggregated in the adventitial layer of the in flamed artery where they were either diffusely distributed or arranged in clusters. The majority of IFN-gamma-secreting T cells expressed CD 25. IFN-gamma(+) T cells included a fraction of cells that had reorgan ized the cytoskeletal protein talin, indicating an interaction of the T cell receptor and an antigen-presenting cell. A subset of IFN-gamma- expressing T cells was undergoing proliferation in the tissue. IFN-gam ma-producing T cells in vasculitic lesions of giant cell arteritis exp ress several markers that identify them as T cells that have recently been stimulated through their antigen-specific receptor. These putativ ely disease-relevant T cells represent only a very minor fraction of t issue-infiltrating cells. Their preferential accumulation in the adven titia is most compatible with the model that they contact the relevant antigen primarily in this particular region of the artery. Their regu latory function appears to extend into the inner media and intima wher e pathological changes in giant cell arteritis are most pronounced.