title: CD8(+) T lymphocytes induce polarized exocytosis of secretory lysosomes by dendritic cells with release of interleukin-1beta and cathepsin D.
abstract: We recently reported that human dendritic cells release the leaderless secretory protein interleukin-1beta (IL-1beta) following specific interaction with alloreactive T lymphocytes. To clarify the molecular mechanism underlying this secretion, this study investigated the intracellular trafficking of IL-1beta in dendritic cells and the signal(s) regulating its release. Results show that a fraction of the intracellular IL-1beta precursor colocalizes with the hydrolase cathepsin D in endolysosomes of dendritic cells; secretion of both proteins is elicited by stimuli that induce intracellular calcium increases. Alloreactive CD8(+) T lymphocytes generate a Ca(++) influx in dendritic cells followed by enrichment in endolysosomes containing IL-1beta and cathepsin D beneath the membrane in contact with T cells. These events result in polarized exocytosis of secretory lysosomes, mediated by microtubules, with release of IL-1beta and cathepsin D toward the interacting CD8(+) T cell.
authors.affiliation: Unit of Protein Biology, Laboratory of Immunology, and Biotechnology Section of Roma, National Cancer Research Institute, 16132 Genoa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Gardella
authors.forename: C
authors.initials: C
authors.lastname: Andrei
authors.forename: L V
authors.initials: LV
authors.lastname: Lotti
authors.forename: A
authors.initials: A
authors.lastname: Poggi
authors.forename: M R
authors.initials: MR
authors.lastname: Torrisi
authors.forename: M R
authors.initials: MR
authors.lastname: Zocchi
authors.forename: A
authors.initials: A
authors.lastname: Rubartelli
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology; D002402:Cathepsin D / Q000378:metabolism*; D002450:Cell Communication; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D005089:Exocytosis / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D008870:Microtubules / Q000187:drug effects / Q000502:physiology; D015739:Nocodazole / Q000494:pharmacology
chemical_list: D007375:Interleukin-1; D002402:Cathepsin D; D015739:Nocodazole; D002118:Calcium