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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/18208

Title: IL-15 Amplifies the Pathogenic Properties of CD4+CD28- T Cells in Multiple Sclerosis
Authors: BROUX, Bieke
Mizee, Mark R.
VANHEUSDEN, Marjan
VAN DER POL, Susanne
VAN HORSSEN, Jack
VAN WIJMEERSCH, Bart
SOMERS, Veerle
DE VRIES, Helga E.
STINISSEN, Piet
HELLINGS, Niels
Issue Date: 2015
Citation: JOURNAL OF IMMUNOLOGY, 194 (5), p. 2099-2109
Abstract: CD4+CD28- T cells arise through repeated antigenic stimulation and are present in diseased tissues of patients with various autoimmune disorders, including multiple sclerosis (MS). These cells are believed to have cytotoxic properties that contribute to the pathogenic damaging of the target organ. Endogenous cues that are increased in the diseased tissue may amplify the activity of CD4+CD28- T cells. In this study, we focused on IL-15, a cytotoxicity-promoting cytokine that is increased in the serum and cerebrospinal fluid of MS patients. Using immunohistochemistry, we demonstrate that IL-15 is mainly produced by astrocytes and infiltrating macrophages in inflammatory lesions of MS patients. Moreover, in vitro transmigration studies reveal that IL-15 selectively attracts CD4+CD28- T cells of MS patients, but not of healthy individuals. IL-15 further induces the expression of chemokine receptors and adhesion molecules on CD4+CD28- T cells, as investigated using flow cytometry, resulting in enhanced migration over a monolayer of human brain endothelial cells. Finally, flow cytometric analyses revealed that IL-15 increases the proliferation and production of GM-CSF, expression of cytotoxic molecules (NKG2D, perforin, and granzyme B), and degranulation capacity of CD4+CD28- T cells. Taken together, these findings indicate that increased peripheral and local levels of IL-15 amplify the pathogenic potential of CD4+CD28- T cells, thus contributing to tissue damage in MS brain lesions.
Notes: Address correspondence and reprint requests to Prof. Niels Hellings, Biomedical Research Institute, Agoralaan, Building C, 3590 Diepenbeek, Belgium. E-mail address: niels.hellings@uhasselt.be
URI: http://hdl.handle.net/1942/18208
DOI: 10.4049/jimmunol.1401547
ISI #: 000350023900011
ISSN: 0022-1767
Category: A1
Type: Journal Contribution
Validation: ecoom, 2016
Appears in Collections: Research publications

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