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http://hdl.handle.net/1942/20247
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DC Field | Value | Language |
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dc.contributor.advisor | STINISSEN, Piet | - |
dc.contributor.advisor | HELLINGS, Niels | - |
dc.contributor.author | BROUX, Bieke | - |
dc.date.accessioned | 2016-01-14T13:39:57Z | - |
dc.date.available | 2016-01-14T13:39:57Z | - |
dc.date.issued | 2013 | - |
dc.identifier.uri | http://hdl.handle.net/1942/20247 | - |
dc.description.abstract | Based on all data gathered in this thesis, combined with findings of other groups, we designed a hypothesis on the possible role of CD4+CD28- T cells in MS (Figure 6.1). In peripheral lymphoid tissues of CMV infected individuals or persons with an (auto-)immune disorder, CD4+ T cells lose CD28 as a result of chronic stimulation (175). This way, CD4+CD28- T cells arise. This cell population has cytotoxic and inflammation-seeking properties and an effector-memory phenotype (168). In the serum of MS patients, IL-15 was shown to be upregulated. We found that IL-15 preferentially induced proliferation of CD4+CD28- T cells, further expanding this cell population. IL-15 also increases the expression of chemokine receptors (including CX3CR1) and adhesion molecules on these cells, potentiating their migratory capacity to the CNS. The levels of both IL-15 and fractalkine are increased in the CNS of MS patients, creating a gradient from the periphery to the CNS. CD4+CD28- T cells migrate via these gradients (mainly fractalkine) to the CNS, crossing the BBB and entering the perivascular space. Here, these cells are reactivated by their cognate antigen (either a myelin or mimetic antigen), resulting in cytokine production. Two of these products, namely IL-1β and IL-6, aid the IL-23 driven differentiation of naive CD4+ T cells to IFN-γ/IL-17A double-producing cells, which are increased in MS lesions. Another product of CD4+CD28- T cells, namely CXCL1, is shown to inhibit remyelination and repair after demyelination. In the perivascular space, infiltrating immune cells (most likely monocytes) express membrane-bound IL-15. This leads to further activation of CD4+CD28- T cells, and upregulation of cytotoxic molecules. When CD4+CD28- T cells enter the brain parenchyma, IL-15 can still be transpresented to them by astrocytes. NKG2D is upregulated in response to IL-15, and NKG2D ligand expressing oligodendrocytes are present in MS lesions (269). In addition to TCR triggering, binding of NKG2D on CD4+CD28- T cells provides costimulation to these cells. This leads to degranulation and secretion of perforin and granzyme B, causing cytolysis of oligodendrocytes expressing NKG2D ligands and consequently, demyelination. | - |
dc.language.iso | en | - |
dc.title | T cell homeostasis: disturbed in autoimmune diseases? | - |
dc.title.alternative | Analyse van CD28null- cellen in auto-immuunziekten | - |
dc.type | Theses and Dissertations | - |
local.format.pages | 195 | - |
local.bibliographicCitation.jcat | T1 | - |
local.type.refereed | Non-Refereed | - |
local.type.specified | Phd thesis | - |
item.accessRights | Open Access | - |
item.contributor | BROUX, Bieke | - |
item.fullcitation | BROUX, Bieke (2013) T cell homeostasis: disturbed in autoimmune diseases?. | - |
item.fulltext | With Fulltext | - |
Appears in Collections: | PhD theses Research publications |
Files in This Item:
File | Description | Size | Format | |
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4154 D-2013-2451-24 BIEKE BROUX.pdf | 11.98 MB | Adobe PDF | View/Open |
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