ACTIVATED T-LYMPHOCYTES INDUCE DEGRANULATION AND CYTOKINE PRODUCTION BY HUMAN MAST-CELLS FOLLOWING CELL-TO-CELL CONTACT

Activated mast cells reside in close apposition to T cells in some inf lammatory processes, In this study, we analyzed whether this close phy sical proximity affects human mast cell degranulation and cytokine rel ease, Thus HMC-1 human mast cells or primary bone marrow-derived human mast cells were cocultured with activated and with resting T cells, M ast cells cocultured with activated T cells released histamine and bet a-hexosaminidase and produced tumor necrosis factor alpha (TNF-alpha), an effect that peaked at 20 h, Kinetics of histamine release parallel ed the formation of heterotypic aggregates, Separation of the two cell populations with a porous membrane prevented mediator release and TNF -alpha production, Addition of the PI3-kinase inhibitor, wortmannin, i nhibited the heterotypic adhesion-associated degranulation but not TNF -alpha production. These data thus indicate a novel pathway through wh ich human mast cells are activated to both release granule-associated mediators and to produce cytokines in association with heterotypic adh esion to activated human T cells.