T cells in healthy ageing and age-associated vasculitides: exploring their phenotype, function and regulation

Upon ageing, changes in the immune system occur. Ageing of the immune system and of T cells in particular are believed to contribute to age-associated vasculitides. Vasculitides are characterized by inflammation of blood vessels. Giant cell arteritis (GCA) is a form of vasculitis which often overlaps with polymyalgia rheumatica (PMR). Both diseases are ageing-related. GCA and PMR patients have inflammation of larger arteries and (peri) articular structures, respectively. Patients often require long-term treatment with glucocorticoids, which have serious side effects. To obtain a better understanding of the pathogenesis of both diseases and to find new clues for treatment, this thesis aimed to explore changes in T-cell phenotype, function and regulation during ageing and in GCA and PMR.
The first results described in this thesis show that immune checkpoints, crucial in activating and controlling T-cell responses, are affected by both age and sex. Differences in T-cell regulation can have consequences for the development of vaccines and for optimisation of immune therapy in which immune checkpoints are targeted.
Furthermore, T cells appeared to be important in the pathogenesis of GCA and PMR as they were present at the site of inflammation in both diseases. CD8+ T cells, a specific subset of T cells, were involved in the pathogenesis of GCA as well. CD8+ T cells were easier to activate after in vitro stimulation and were local producers of pro-inflammatory cytokines. Also, CD8+ T cells in the tissues of GCA patients may skew macrophages to a pro-inflammatory phenotype via the production of GM-CSF.