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

J Immunol. 1995 Oct 15;155(8):3801-5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / physiology
  • Antigens, CD / genetics*
  • Antigens, CD / immunology
  • Dermatitis, Contact / etiology
  • Dermatitis, Contact / genetics*
  • Dermatitis, Contact / immunology
  • Female
  • Immunosuppression Therapy* / methods
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Receptors, Tumor Necrosis Factor / genetics*
  • Receptors, Tumor Necrosis Factor / immunology
  • Receptors, Tumor Necrosis Factor, Type I
  • Ultraviolet Rays*

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I