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Adenovirus‐mediated blockade of lymphotoxin‐β inhibits the induction of contact sensitivity in mice
Author(s) -
Trueb Ralph M.,
Brown Geri R.,
Dougherty Irene,
ValdezSilva Maria,
Cruz Ponciano D.
Publication year - 1997
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.1997.tb00202.x
Subject(s) - lymphotoxin , lymphotoxin beta receptor , tumor necrosis factor alpha , lymphotoxin alpha , receptor , immunology , chemistry , pharmacology , medicine
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 dinitro‐fluorobenzene. 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.