Lymphotoxin-β Receptor Activation by Activated T Cells Induces Cytokine Release from Mouse Bone Marrow-Derived Mast Cells

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Abstract
Lymphotoxin-β receptor (LTβR) signaling is known to play a key role in embryonic lymphoid organ formation as well as maintenance of lymphoid architecture. Activation of the LTβR is induced by either the heterotrimeric lymphotoxin-α1β2 (LTα1β2) or the homotrimeric LIGHT (homologous to lymphotoxins, exhibits inducible expression, and competes with HSV gpD for herpes virus entry mediator, a receptor expressed by T lymphocyte). Both ligands are expressed on activated lymphocytes. As mast cells reside in close proximity to activated T cells in some inflammatory tissues, we examined the expression of LTβR on bone marrow-derived mast cells and asked whether the LTβR-ligand interaction would allow communication between mast cells and activated T cells. We found that mast cells express LTβR at the mRNA as well as at the protein level. To investigate LTβR-specific mast cell activation, the LTβR on BMMC from either wild-type or LTβR-deficient mice was stimulated with recombinant mouse LIGHT or agonistic mAbs in the presence of ionomycin. LTβR-specific release of the cytokines IL-4, IL-6, TNF, and the chemokines macrophage inflammatory protein 2 and RANTES was detected. Moreover, coculture of mast cells with T cells expressing the LTβR ligands also entailed the release of these cytokines. Interference with a specific LTβR inhibitor resulted in significant suppression of mast cell cytokine release. These data clearly show that LTβR expressed on mast cells can transduce a costimulatory signal in T cell-dependent mast cell activation.