Effect of gene-targeted mutation in TNF receptor (p55) on contact hypersensitivity and ultraviolet B-induced immunosuppression

Abstract

Tumor necrosis factor α (TNF-α) is a pleiotropic proinflammatory cytokine. TNF-α 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-α on contact hypersensitivity (CHS). To determine the role of TNF-α in the generation and regulation of CHS, gene-targeted mutant mice lacking TNF-receptor (p55) gene (TNF-R1(-) mice) were treated with dinitrofluorobenzene (DNF8) to induce CHS. TNF-R1(-) mice showed significant hyperresponsiveness in CHS (152.8 ± 20.9%, p < 0.025) compared with normal syngeneic mice (C578L/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 UV8 and 3 days later they were painted with 0.5% DNF8 (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-α 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-α plays a regulatory role in CHS but is not required to induce UVB-mediated immunosuppression.