POS0112 CD8+ T-CELL INFILTRATION IS ASSOCIATED WITH LESIONAL GM-CSF OVEREXPRESSION IN GCA

Abstract

Background:Giant cell arteritis (GCA) is a large-vessel vasculitis characterized by granulomatous T cell- and macrophage infiltration. Granulocyte-macrophage colony stimulating factor (GM-CSF) is present in GCA-affected vessels where it may be involved in skewing of tissue destructive macrophages (1). Furthermore, a recent phase 2 clinical trial demonstrated that GM-CSF receptor blockade was superior to placebo at 26 weeks in GCA. However, the cellular source of GM-CSF in GCA is still unclear.Objectives:As T cells have been identified as a major source of GM-CSF in other immune-mediated diseases such as multiple sclerosis, we investigated whether T cells are GM-CSF producers in GCA patients, both systemically and locally.Methods:GM-CSF production capacity by PMA-stimulated PBMCs from newly diagnosed, untreated GCA patients and HCs (N=10 each) was assessed using flow cytometry. Temporal artery biopsies (TABs, N=5) were immunohistochemically stained for CD3, CD8 and GM-CSF. Colocalization of these markers was assessed with immunofluorescence.Results:Proportions of CD4+ (median GCA=3.1%; HCs=2.76%) and CD8+ (median GCA=5.8%; HCs=5.8%) T cells produced GM-CSF after in vitro stimulation, but no significant differences were found between the groups. Immunofluorescence staining confirmed that CD3+ T cells (both CD8+ and CD8-) were positive for GM-CSF in TABs. Interestingly, GM-CSF positivity in TABs correlated strongly with the extent of CD8+ T-cell infiltration (r=0.74, p<0.01), but not with CD3+ T-cell infiltration (r=0.38, p=0.16).Conclusion:Our data imply that T cells are an important source of GM-CSF in GCA lesions. The correlation of the extent of CD8+ T-cell infiltration with GM-CSF positivity suggests that CD8+ T cells are the major source of local GM-CSF overexpression in tissue.