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 factor ligand family. Recent studies have suggested a role for this cytokine 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 the extracellular domain of the lymphotoxin-beta receptor fused to IgG heavy chain. Intravenous injection of the recombinant virus into BALB/c mice yielded plasma levels of inhibitor protein > 500 micrograms that persisted for 1 week. Mice treated in this manner were compared with control animals injected with adenovirus encoding beta-galactosidase, with respect to their ability to mount contact sensitivity responses to epicutaneously applied dinitro-fluorobenzene. Mice transduced with the lymphotoxin-beta inhibitor prior to the induction of contact sensitivity showed significantly suppressed ear swelling responses. By contrast, mice treated with the lymphotoxin-beta inhibitor prior to the elicitation 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 sensitivity response.
Trueb
R M
RM
Department of Dermatology, University of Zurich.
Brown
G R
GR
Dougherty
I
I
Valdez-Silva
M
M
Cruz
P D
PD
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D003877:Dermatitis, Contact / Q000209:etiology* / Q000517:prevention & control*; D005260:Female; D053259:Lymphotoxin beta Receptor; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D011994:Recombinant Proteins / Q000097:blood / Q000494:pharmacology; D014764:Viral Proteins / Q000097:blood / Q000494:pharmacology
C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014764:Viral Proteins