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

Abstract

We recently reported that mast cells stimulated via FcεRI aggregation can enhance T cell activation by a TNF-dependent mechanism. However, the molecular mechanisms responsible for such IgE-, Ag- (Ag-), and mast cell-dependent enhancement of T cell activation remain unknown. In this study we showed that mouse bone marrow-derived cultured mast cells express various costimulatory molecules, including members of the B7 family (ICOS ligand (ICOSL), PD-L1, and PD-L2) and the TNF/TNFR families (OX40 ligand (OX40L), CD153, Fas, 4-1BB, and glucocorticoid-induced TNFR). ICOSL, PD-L1, PD-L2, and OX40L also are expressed on APCs such as dendritic cells and can modulate T cell function. We found that IgE- and Ag-dependent mast cell enhancement of T cell activation required secreted TNF; that TNF can increase the surface expression of OX40, ICOS, PD-1, and other costimulatory molecules on CD3+ T cells; and that a neutralizing Ab to OX40L, but not neutralizing Abs to ICOSL or PD-L1, significantly reduced IgE/Ag-dependent mast cell-mediated enhancement of T cell activation. These results indicate that the secretion of soluble TNF and direct cell-cell interactions between mast cell OX40L and T cell OX40 contribute to the ability of IgE- and Ag-stimulated mouse mast cells to enhance T cell activation.

Is there a role for mast cells in psoriasis?

“…In co-cultures of mouse mast cells and T cells, both cell-cell proximity and soluble factors, especially TNF, can contribute to T cell proliferation, and mast cells can activate multiple T cell subsets, such as CD4 + , CD8 + , Th1, Th2, Tc1, Tc2, TCR + and CD4 + CD62L ¡ T cells [124]. The same group demonstrated later that this mast cell-induced enhancement of T cell activation is signiWcantly dependent on the secretion of soluble TNF and direct cell-cell interactions between mast cell OX40 ligand and T cell OX40 receptor [125]. Similarly, human mast cells have been shown to activate T cells in vitro by direct cross-talk between OX40 ligand on mast cells and OX40 receptor on T cells [90].…”

Fasciola hepatica Tegumental Coat Impairs Mast Cells’ Ability To Drive Th1 Immune Responses

“…OX40L, CD40L, CD28, and ICAM1 are thought to have a critical role in mast cell-T cell communication (33)(34)(35). BMMCs and PCMCs express low levels of OX40L, CD40L, and CD28 (data not shown), and these were not significantly enhanced in the presence of LPS and BP.…”

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

“…Co-stimulatory molecules expressed by mouse and/ or human mast cells include members of the B7 family, members of tumour-necrosis factor (TNF)-TNF receptor families, CD28 and CD40 ligand (CD40L) 6,13,46,47 . Moreover, mast cells can exhibit costimulatory function in vitro.…”

“…Moreover, mast cells can exhibit costimulatory function in vitro. For example, engagement of the costimulatory ligand OX40L expressed by human 46 or mouse 47 mast cells and OX40 expressed by T cells is required for optimal mast-cell-dependent enhancement of T-cell proliferation 46,47 or cytokine production 47 .…”

“…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.…”