Interleukin 15 is produced by endothelial cells and increases the transendothelial migration of T cells in vitro and in the SCID mouse-human rheumatoid arthritis model in vivo

Nancy Oppenheimer-Marks, Ruth I. Brezinschek, Mansour Mohamadzadeh, Randi Vita, Peter E. Lipsky

Research output: Contribution to journalArticlepeer-review

161 Scopus citations

Abstract

The capacity of endothelial cells (EC) to produce IL-15 and the capacity of IL-15 to influence transendothelial migration of T cells was examined. Human umbilical vein endothelial cells expressed both IL-15 mRNA and protein. Moreover, endothelial-derived IL-15 enhanced transendothelial migration of T cells as evidenced by the inhibition of this process by blocking monoclonal antibodies to IL-15. IL-15 enhanced transendothelial migration of T cells by activating the binding capacity of the integrin adhesion molecule LFA-1 (CD11a/CD18) and also increased T cell motility. In addition, IL-15 induced expression of the early activation molecule CD69. The importance of IL-15 in regulating migration of T cells in vivo was documented by its capacity to enhance accumulation of adoptively transferred human T cells in rheumatoid arthritis synovial tissue engrafted into immune deficient SCID mice. These results demonstrate that EC produce IL-15 and imply that endothelial IL-15 plays a critical role in stimulation of T cells to extravasate into inflammatory tissue.

Original languageEnglish (US)
Pages (from-to)1261-1272
Number of pages12
JournalJournal of Clinical Investigation
Volume101
Issue number6
DOIs
StatePublished - Mar 15 1998
Externally publishedYes

Keywords

  • Adhesion
  • CD69
  • Cytokine
  • LFA-1
  • Motility

ASJC Scopus subject areas

  • General Medicine

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