Autoimmune rheumatologic diseases
Giant cell arteritis (GCA) is the most common vasculitis in adults affecting large and medium-sized arteries. It can cause of blindness and stroke. IL-6 and T cell accumulation within the arterial wall contributes to the development of GCA, and blockade of IL-6 activity is efficacious in its treatment. We examined the relationship between levels of IL-6 and immunological processes that control the expansion of T cells within GCA lesions. The expression of IL-6 RNA was quantified by RT-qPCR in 14 GCA-positive temporal artery biopsies and examined in relation to the frequency of proliferating CD4 T cells (identified by immunohistochemistry [IHC] for CD4 and Ki67), T regs (identified by IHC for Foxp3), and T cells undergoing apoptotic cell death (identified by IHC for CD4 and cleaved caspase-3). There was a significant positive correlation between the expression of IL-6 and increased frequency of proliferating CD4 T cells (r = 0.56, p < 0.05). The expansion of T cells can be inhibited by T regs but IL-6 expression was not correlated with differences in T reg accumulation. IL-6 levels were also not significantly correlated with differences in apoptotic death of CD4 T cells, although there was a trend toward a negative correlation. In summary, IL-6 may contribute to the accumulation of CD4 T cells in GCA by supporting their proliferation within the arterial wall through mechanisms that are independent of effects on T reg expansion.
University of British Columbia
Arthritis Research Canada
Simon Fraser University