Lymphotoxin-beta receptor activation by activated T cells induces cytokine release from mouse bone marrow-derived mast cells.
Lymphotoxin-beta receptor (LTbetaR) signaling is known to play a key role in embryonic lymphoid organ formation as well as maintenance of lymphoid architecture. Activation of the LTbetaR is induced by either the heterotrimeric lymphotoxin-alpha(1)beta(2) (LTalpha(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 LTbetaR on bone marrow-derived mast cells and asked whether the LTbetaR-ligand interaction would allow communication between mast cells and activated T cells. We found that mast cells express LTbetaR at the mRNA as well as at the protein level. To investigate LTbetaR-specific mast cell activation, the LTbetaR on BMMC from either wild-type or LTbetaR-deficient mice was stimulated with recombinant mouse LIGHT or agonistic mAbs in the presence of ionomycin. LTbetaR-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 LTbetaR ligands also entailed the release of these cytokines. Interference with a specific LTbetaR inhibitor resulted in significant suppression of mast cell cytokine release. These data clearly show that LTbetaR expressed on mast cells can transduce a costimulatory signal in T cell-dependent mast cell activation.
Stopfer
Peter
P
Department of Immunology, University of Regensburg, Franz-Josef-Strauss Allee 11, 93042 Regensburg, Germany.
Männel
Daniela N
DN
Hehlgans
Thomas
T
D000818:Animals; D001854:Bone Marrow Cells; D002450:Cell Communication; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism*; D008024:Ligands; D008213:Lymphocyte Activation; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha / Q000378:metabolism; D008407:Mast Cells / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology*; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D008024:Ligands; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha