title: Effect of gene-targeted mutation in TNF receptor (p55) on contact hypersensitivity and ultraviolet B-induced immunosuppression.
abstract: Tumor necrosis factor alpha (TNF-alpha) is a pleiotropic proinflammatory cytokine. TNF-alpha has been implicated in the pathogenesis of delayed-type hypersensitivity reactions such as allergic contact hypersensitivity and has been suggested as a mediator of ultraviolet B (UVB)-induced immunosuppression. Conflicting reports, however, exist concerning the effects of TNF-alpha on contact hypersensitivity (CHS). To determine the role of TNF-alpha in the generation and regulation of CHS, gene-targeted mutant mice lacking TNF-receptor (p55) gene (TNF-R1(-) mice) were treated with dinitrofluorobenzene (DNFB) to induce CHS. TNF-R1(-) mice showed significant hyperresponsiveness in CHS (152.8 +/- 20.9%, p < 0.025) compared with normal syngeneic mice (C57BL/6) assessed by ear swelling. To determine whether UVB can induce suppression in TNF-R1(-) mice, mice were irradiated on the shaved abdomen with 96 mj/cm2 UVB and 3 days later they were painted with 0.5% DNFB (sensitization dose), followed 5 days later with 0.2% DNFB to the left ear (challenge dose). Significant suppression of CHS was observed both locally (sensitization on irradiated site) and systemically (sensitization on unirradiated site) in UVB-irradiated TNF-R1(-) mice as well as in normal mice. To rule out possible signaling through p75 TNF-R, the mice were treated with anti-TNF-alpha Ab (V1q), which can neutralize any TNF effects through either receptor. V1q had no effect on these phenomena observed in TNF-R1(-) mice. These results suggest that TNF-alpha plays a regulatory role in CHS but is not required to induce UVB-mediated immunosuppression.
authors.affiliation: Division of Dermatology, Sunnybrook Health Science Centre, University of Toronto, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Kondo
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Fujisawa
authors.forename: G M
authors.initials: GM
authors.lastname: Shivji
authors.forename: B
authors.initials: B
authors.lastname: Echtenacher
authors.forename: T W
authors.initials: TW
authors.lastname: Mak
authors.forename: D N
authors.initials: DN
authors.lastname: Sauder
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D003877:Dermatitis, Contact / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D005260:Female; D007165:Immunosuppression Therapy / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000276:immunology; D047888:Receptors, Tumor Necrosis Factor, Type I; D014466:Ultraviolet Rays
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I