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*
Division of Gastroenterology and Hepatology and
Division of General Internal Medicine, Department of Medicine,
Department of Pathology, and
§
Department of Plastic and Reconstructive Surgery, University Hospital Innsbruck, Innsbruck, Austria; and
¶
Pulmonary Center, Boston University School of Medicine, Boston, MA 01226
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-
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.
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