Publication
Title
B Cell-Derived IL-15 Enhances CD8 T Cell Cytotoxicity and Is Increased in Multiple Sclerosis Patients
Author
Abstract
Multiple lines of evidence suggest that CD8 T cells contribute to the pathogenesis of multiple sclerosis (MS). However, the sources and involvement of cytokines such as IL-15 in activating these cells is still unresolved. To investigate the role of IL-15 in enhancing the activation of CD8 T cells in the context of MS, we determined cell types expressing the bioactive surface IL-15 in the peripheral blood of patients and evaluated the impact of this cytokine on CD8 T cell cytotoxicity and migration. Flow cytometric analysis showed a significantly greater proportion of B cells and monocytes from MS patients expressing IL-15 relative to controls. We established that CD40L activation of B cells from healthy donors increased their IL-15 levels, reaching those of MS patients. We also demonstrated an enhanced cytotoxic profile in CD8 T cells from MS patients upon stimulation with IL-15. Furthermore, we showed that IL-15 expressed by B cells and monocytes is sufficient and functional, enhancing granzyme B production by CD8 T cells upon coculture. Exposure of CD8 T cells to this cytokine enhanced their ability to kill glial cells as well as to migrate across an in vitro inflamed human blood–brain barrier. The elevated levels of IL-15 in patients relative to controls, the greater susceptibility of CD8 T cells from patients to IL-15, in addition to the enhanced cytotoxic responses by IL-15–exposed CD8 T cells, stresses the potential of therapeutic strategies to reduce peripheral sources of IL-15 in MS.
Language
English
Source (journal)
The journal of immunology. - Baltimore, Md
Publication
Baltimore, Md : 2011
ISSN
0022-1767 [Print]
1550-6606 [Online]
DOI
10.4049/JIMMUNOL.1100885
Volume/pages
187 :8 (2011) , p. 4119-4128
ISI
000295623100024
Full text (Publisher's DOI)
UAntwerpen
Publication type
Subject
External links
Web of Science
Record
Identifier
Creation 26.09.2023
Last edited 14.10.2023
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