Mast cells enhance T cell activation: Importance of mast cell-derived TNF

Abstract

Mast cells are not only important effector cells in immediate hypersensitivity reactions and immune responses to pathogens but also can contribute to T cell-mediated disorders. However, the mechanisms by which mast cells might influence T cells in such settings are not fully understood. We find that mast cells can enhance proliferation and cytokine production in multiple T cell subsets. Mast cell-dependent enhancement of T cell activation can be promoted by FcRI-dependent mast cell activation, TNF production by both mast cells and T cells, and mast cell-T cell contact. However, at high concentrations of cells, mast cells can promote T cell activation independent of IgE or TNF. Finally, mast cells also can promote T cell activation by means of soluble factors. These findings identify multiple mechanisms by which mast cells can influence T cell proliferation and cytokine production.allergy ͉ asthma ͉ autoimmunity ͉ cytokines ͉ immune response

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

“…1-3 suggest that mast cells may be able to act as accessory cells to promote T cell activation through the expression of several different costimulatory molecules. However, we recently reported that mast cells can promote T cell activation, such as proliferation and cytokine production, by at least one mechanism that requires proximity between T cells and mast cells as well as by the production of soluble factors (27). We also showed that one pathway by which IgE-and Ag-activated mast cells could stimulate T cells was by production of TNF (27).…”

“…We recently reported that mouse mast cells can significantly enhance T cell proliferation and cytokine production by at least two mechanisms, one of which is dependent on the activation of mast cells via the Fc⑀RI and requires mast cell-derived TNF (27). Although we showed that this pathway of mast cell-dependent enhancement of T cell activation is favored by proximity between mast cells and T cells, the molecular mechanisms underlying this mast cell-T cell interaction were not identified, nor was it clear to what extent soluble TNF, as opposed to membrane-associated TNF, contributed to the important role of TNF in mast cell-dependent T cell activation.…”

“…T cells were cocultured with BMCMCs as described previously (27). BMCMCs were sensitized with 1 g/ml H1-⑀-26 IgE anti-DNP mAb (30) at 37°C overnight.…”

“…For pretreatment of T cells with rmTNF, C57BL/6-CD3 ϩ T cells (2 ϫ 10 6 cells/well in a 12-well plate) were cultured with 0.3 g/ml plate-coated anti-CD3 with or without rmTNF (PeproTech) at 37°C for 72 h. Then T cells pretreated with or without TNF were washed, and 0.25 or 0.03 ϫ 10 5 T cells/well were cocultured with mitomycin C-treated, IgE-sensitized or nonsensitized BMCMCs (0.25 or 0.03 ϫ 10 5 cells/well) in the presence or the absence of 1.0 or 0.03 g/ml anti-CD3 mAb and in the presence or the absence of 5 ng/ml DNP-HSA, but without additional rmTNF, at 37°C for 72 h, as described above. In some coculture experiments, T cells and mast cells were separated by a Transwell membrane as described previously (27 …”

Immunomodulatory mast cells: negative, as well as positive, regulators of immunity

“…Mast cells represent potential sources of many mediators that can enhance or suppress the development, survival, proliferation, migration, maturation, or function of immune cells (reviewed in REFS [1][2][3][5][6][7][8]13,[16][17][18]21,30,31,43,44,[46][47][48][49][50][51][52][53][54][55][56]. Some individual mediators, such as histamine, can have both positive and negative immunomodulatory effects.…”