Effect of gene-targeted mutation in TNF receptor (p55) on contact hypersensitivity and ultraviolet B-induced immunosuppression
Kondo, S.; Wang, B.; Fujisawa, H.; Shivji, G.M.; Echtenacher, B.; Mak, T.W.; Sauder, D.N.
Journal of Immunology 155(8): 3801-3805
1995
ISSN/ISBN: 0022-1767 PMID: 7561085 Document Number: 444363
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 lt 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/cm-2 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-a 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.