Activated T lymphocytes induce degranulation and cytokine production by human mast cells following cell-to-cell contact

Abstract

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 ␤-hexosaminidase and produced tumor necrosis factor ␣ (TNF-␣), 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-␣ production. Addition of the PI3-kinase inhibitor, wortmannin, inhibited the heterotypic adhesion-associated degranulation but not TNF-␣ 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.

Increased Density of Interstitial Mast Cells in Amyloid A Renal Amyloidosis

“…Previous studies have also shown that MC maturation and activation is regulated by various products (interleukin-3 and 4) of T-lymphocytes (26), whereas MC derivatives such as histamine, tryptase, chymase, TNF-␣, and interleukins enhance inflammatory cell transmigration, maturation, and cytokine-release (2,27). Previous reports suggested the involvement of apoptosis of either renal host cells (28) or T-cells (29) in the pathogenesis of both human and experimental renal amyloidosis.…”

Mast Cells Enhance T Cell Activation: Importance of Mast Cell Costimulatory Molecules and Secreted TNF

“…For example, purified populations of mast cells can present Ags to T cells by either MHC class I-or class II-restricted mechanisms in vitro (8 -11), and contact with activated T cells in vitro can induce some mast cell populations to secrete histamine, TNF, and metalloproteinase 9 and to exhibit enhanced levels of IL-4 mRNA (12)(13)(14)(15). Besides representing a major potential source of TNF (16,17), which can have several effects that influence T cell recruitment, activation, and function (18 -21), at least some mast cells can produce many other factors, including CCL2, CCL3, CCL4, CCL5, XCL1, IL-16, and leukotriene B 4 , which also have the potential to enhance T cell recruitment to local inflammatory sites (5,(22)(23)(24)(25).…”

Activation of Mast Cells by Trimeric G Protein Gi3; Coupling to the A3 Adenosine Receptor Directly and upon T Cell Contact

“…Such conditions can be induced by exposing mast cells to activated T cells. Specifically, we have previously demonstrated that direct and prolonged contact between HMCs and PMA-activated T cells induces mast cell activation, resulting in degranulation and release of cytokines (17), metalloproteinases (9), and fibrotic factors such oncostatin-M (18). We further showed that contact with membranes derived from activated T cells suffices to achieve maximal activation (9).…”