B cell-derived IL-15 enhances CD8 T cell cytotoxicity and is increased in multiple sclerosis patients

Raphael Schneider, Alma Nazlie Mohebiany, Igal Ifergan, Diane Beauseigle, Pierre Duquette, Alexandre Prat, Nathalie Arbour*

*Corresponding author for this work

Research output: Contribution to journalArticle

35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4119-4128
Number of pages10
JournalJournal of Immunology
Volume187
Issue number8
DOIs
StatePublished - Oct 15 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'B cell-derived IL-15 enhances CD8 T cell cytotoxicity and is increased in multiple sclerosis patients'. Together they form a unique fingerprint.

  • Cite this

    Schneider, R., Mohebiany, A. N., Ifergan, I., Beauseigle, D., Duquette, P., Prat, A., & Arbour, N. (2011). B cell-derived IL-15 enhances CD8 T cell cytotoxicity and is increased in multiple sclerosis patients. Journal of Immunology, 187(8), 4119-4128. https://doi.org/10.4049/jimmunol.1100885