A role for IL-16 in the cross-talk between dendritic cells and T cells.
Dendritic cells (DCs) in the periphery capture and process Ags, migrate to lymphoid organs, and initiate immune responses in T cells. IL-16, the soluble ligand for CD4, is a potent chemoattractant for CD4+ T cells, eosinophils, and monocytes and is mainly derived from activated T cells. Because migration is a fundamental property of DCs, we asked whether IL-16 induces chemotaxis in DCs and whether DCs are a source of IL-16. DCs were generated by culture of monocytes in IL-4 and GM-CSF for 6 days and subsequently highly purified employing magnetic beads. Migration was assayed by nitrocellulose and polycarbonate filter-based assays, and distinction of chemotaxis and chemokinesis was performed by a checkerboard analysis. Messenger RNA and protein data revealed constitutive expression and release of IL-16 by day-6 DCs. Gradients of rIL-16 induced a chemotactic response of DCs. Furthermore, the chemotactic activity of DC supernatant toward DCs themselves and T cells was mainly due to IL-16, because the addition of neutralizing Abs completely abrogated the migratory response. However, after induction of maturation by the addition of TNF-alpha and PGE2 DCs, neither expressed IL-16 mRNA nor produced IL-16 protein. We conclude that IL-16 may play a role in the trafficking of DCs and may be a major chemotactic signal from DCs toward themselves and toward T cells.
Kaser
A
A
Division of Gastroenterology, Department of Medicine, University Hospital Innsbruck, Austria.
Dunzendorfer
S
S
Offner
F A
FA
Ryan
T
T
Schwabegger
A
A
Cruikshank
W W
WW
Wiedermann
C J
CJ
Tilg
H
H
D002450:Cell Communication / Q000276:immunology*; D002474:Cell-Free System / Q000276:immunology; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000502:physiology; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D019410:Interleukin-16 / Q000096:biosynthesis / Q000502:physiology*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism
D002630:Chemotactic Factors; D019410:Interleukin-16; D014443:Tyrosine