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 inflammatory processes, In this study, we analyzed whether this close physical proximity affects human mast cell degranulation and cytokine release, Thus HMC-1 human mast cells or primary bone marrow-derived human mast cells were cocultured with activated and with resting T cells, Mast cells cocultured with activated T cells released histamine and beta-hexosaminidase and produced tumor necrosis factor alpha (TNF-alpha), an effect that peaked at 20 h, Kinetics of histamine release paralleled 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, inhibited the heterotypic adhesion-associated degranulation but not TNF-alpha production. These data thus indicate a novel pathway through which human mast cells are activated to both release granule-associated mediators and to produce cytokines in association with heterotypic adhesion to activated human T cells.