Lymphotoxin-β is a newly recognized member of the tumor necrosis factor ligand family. Recent studies have suggested a role for this cytokine in delayed-type hypersensitivity responses. To determine whether lymphotoxin-β contributes to the development of contact sensitivity, we utilized an inhibitor protein that can effectively block binding of lymphotoxin-β to its receptor. An adenoviral vector was created that encodes for a lymphotoxin-β inhibitor protein consisting of the extracellular domain of the lymphotoxin- β receptor fused to IgG heavy chain. Intravenous injection of the recombinant virus into BALB/c mice yielded plasma levels of inhibitor protein >500 μg that persisted for 1 week. Mice treated in this manner were compared with control animals injected with adenovirus encoding β-galactosidase, with respect to their ability to mount contact sensitivity responses to epicutaneously applied dinitrofluorobenzene. Mice transduced with the lymphotoxin-β inhibitor prior to the induction of contact sensitivity showed significantly suppressed ear swelling responses. By contrast, mice treated with the lymphotoxin-β inhibitor prior to the elicitation of contact sensitivity showed no change in ear swelling responses in comparison to controls. These findings indicate that lymphotoxin-β plays an important role in the afferent phase of the contact sensitivity response.
|Original language||English (US)|
|Number of pages||6|
|State||Published - 1997|
- Adenovirus-mediated inhibitor gene transfer
- Contact sensitivity
ASJC Scopus subject areas
- Molecular Biology