Title: Genetische en cellulaire karakterisatie van Foxp3+ regulatoire T-cellen in ziekte en gezondheid
Other Titles: Genetic and cellular characterisation of Foxp3+ regulatory T cells during health and disease
Authors: Pierson, Wim
Issue Date: 20-Oct-2014
Abstract: Regulatory T cells (Treg) are indispensible for the prevention of devastating immune dysregulation. The work described in this thesis provides a unique new insight into regulatory T cell biology demonstrating that after partial Treg depletion, levels of IL-2 rise significantly, allowing the unaffected Treg not only to survive but also to rapidly repopulate the niche in a co-stimulation dependent manner, with a temporary overshoot in numbers. From the detailed study of the Bcl-2 family of apoptosis/survival regulators we found that Mcl-1 and Bim are essential for regulating Treg survival and apoptosis, respectively, while Bcl-XL and Bcl-2 are not. From the finding that Mcl-1 expression is influenced by IL-2 availability, we have uncovered a potential mechanism by which IL-2 is capable of regulating apoptosis levels during perturbations in the size of the Treg niche. In addition, we found that thymus-derived Treg are able to participate in a germinal centre (GC) response by adopting a phenotype reminiscent of the cells they were found to regulate: the follicular T helper subset (Tfh). We show that follicular Treg (Tfr) limit the size of the Tfh pool, thereby limiting the help to GC B cells and ensuring the generation of high affinity antibodies and protective B cell memory.
Publication status: published
KU Leuven publication type: TH
Appears in Collections:Laboratory of Genetics of Autoimmunity
Laboratory of Immunobiology (Rega Institute)

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