ADENOVIRUS-MEDIATED BLOCKADE OF LYMPHOTOXIN-BETA INHIBITS THE INDUCTION OF CONTACT SENSITIVITY IN MICE

Lymphotoxin-beta is a newly recognized member of the tumor necrosis fa ctor ligand family. Recent studies have suggested a role for this cyto kine in delayed-type hypersensitivity responses. To determine whether lymphotoxin-beta contributes to the development of contact sensitivity , we utilized an inhibitor protein that can effectively block binding of lymphotoxin-beta to its receptor. An adenoviral vector was created that encodes for a lymphotoxin-beta inhibitor protein consisting of th e extracellular domain of the lymphotoxin-beta receptor fused to IgG h eavy chain. Intravenous injection of the recombinant virus into BALB/c mice yielded plasma levels of inhibitor protein >500 mu g that persis ted for 1 week. Mice treated in this manner were compared with control animals injected with adenovirus encoding beta-galactosidase, with re spect to their ability to mount contact sensitivity responses to epicu taneously applied dinitro-fluorobenzene. Mice transduced with the lymp hotoxin-beta inhibitor prior to the induction of contact sensitivity s howed significantly suppressed ear swelling responses. By contrast, mi ce treated with the lymphotoxin-beta inhibitor prior to the elicitatio n of contact sensitivity showed no change in ear swelling responses in comparison to controls. These findings indicate that lymphotoxin-beta plays an important role in the afferent phase of the contact sensitiv ity response.