T Cell Proliferation by Direct Cross-Talk between OX40 Ligand on Human Mast Cells and OX40 on Human T Cells: Comparison of Gene Expression Profiles between Human Tonsillar and Lung-Cultured Mast Cells

Abstract

Mast cells (MCs) are the primary effector cells in allergic reactions and have also been found to activate T cells and to reside in close physical proximity to T cells. However, the molecular mechanisms involved in the MC-T cell interaction remain unclear. We hypothesized that human tonsillar MCs, which locate in the interfollicular areas, might interact with T cells. Thus, we first established a culture system of human tonsillar MCs and then compared gene expression profiles of tonsillar MCs with that of lung MCs before and after aggregation of FcεRI by using high-density oligonucleotide probe arrays. Here we show that resting tonsillar MCs, when compared with lung MCs, revealed significantly higher expression levels for CC chemokines (CCL3 and 4), which recruit T cells, and for TNFR superfamilies (OX40 ligand and 4-1BB ligand), which induce proliferation of T cells. After aggregation of FcεRI, not only tonsillar MCs but also lung MCs up-regulated the expression of these molecules. We confirmed that T cell proliferation is induced in direct cross-talk by the MC surface molecule OX40 ligand. These results suggest that human MCs may play important roles in adaptive immunity through the T cell responses.

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.…”

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

“…Although such costimulatory molecules are generally thought to have roles in DC-associated T cell activation, Kashiwakura et al (26) reported that human tonsil mast cell-OX40L can contribute to the T cell proliferation induced when human T cells are incubated with mast cells that have undergone Fc⑀RI-dependent activation in vitro.…”

“…However, certain mast cell populations, in addition to having the capacity to produce soluble factors that can influence T cell biology, can express costimulatory molecules such as OX40 ligand (OX40L) and 4-1BBL (22,26). Although such costimulatory molecules are generally thought to have roles in DC-associated T cell activation, Kashiwakura et al (26) reported that human tonsil mast cell-OX40L can contribute to the T cell proliferation induced when human T cells are incubated with mast cells that have undergone Fc⑀RI-dependent activation in vitro.…”