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The Journal of Immunology, 2004, 172: 7459-7465.
Copyright © 2004 by The American Association of Immunologists

Lymphotoxin-{beta} Receptor Activation by Activated T Cells Induces Cytokine Release from Mouse Bone Marrow-Derived Mast Cells1

Peter Stopfer, Daniela N. Männel and Thomas Hehlgans2

Department of Immunology, University of Regensburg, Regensburg, Germany

Lymphotoxin-{beta} receptor (LT{beta}R) signaling is known to play a key role in embryonic lymphoid organ formation as well as maintenance of lymphoid architecture. Activation of the LT{beta}R is induced by either the heterotrimeric lymphotoxin-{alpha}1{beta}2 (LT{alpha}1{beta}2) 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 LT{beta}R on bone marrow-derived mast cells and asked whether the LT{beta}R-ligand interaction would allow communication between mast cells and activated T cells. We found that mast cells express LT{beta}R at the mRNA as well as at the protein level. To investigate LT{beta}R-specific mast cell activation, the LT{beta}R on BMMC from either wild-type or LT{beta}R-deficient mice was stimulated with recombinant mouse LIGHT or agonistic mAbs in the presence of ionomycin. LT{beta}R-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 LT{beta}R ligands also entailed the release of these cytokines. Interference with a specific LT{beta}R inhibitor resulted in significant suppression of mast cell cytokine release. These data clearly show that LT{beta}R expressed on mast cells can transduce a costimulatory signal in T cell-dependent mast cell activation.




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