CD8+ T lymphocytes induce polarized exocytosis of secretory lysosomes by dendritic cells with release of interleukin-1-Beta and cathepsin D

We recently reported that human dendritic cells release the leaderless secretary protein Interleukin-1 beta (IL-1 beta) following specific Interaction with alloreactive T lymphocytes. To clarity the molecular mechanism underlying this secretion, this study investigated the intracellular trafficking of IL-1 beta in dendritic cells and the signal(s) regulating its release. Results show that a fraction of the intracellular IL-1 beta 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-1 beta and cathepsin D beneath the membrane In contact with T cells. These events result in polarized exocytosis of secretary lysosomes, mediated by microtubules, with release of IL-1 beta and cathepsin D toward the interacting CD8(+) T cell. (C) 2001 by The American Society of Hematology.