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


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    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.
    Originele taal-2English
    KwalificatieDoctor of Philosophy
    Toekennende instantie
    • Rijksuniversiteit Groningen
    • Brouwer, Liesbeth, Supervisor
    • Boots, Mieke, Supervisor
    • Heeringa, Peter, Supervisor
    • van der Geest, Niels, Co-supervisor
    Datum van toekenning16-mrt.-2022
    Plaats van publicatie[Groningen]
    Gedrukte ISBN's978-94-6421-650-9
    StatusPublished - 2022

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