The Journal of Immunology, Vol 155, Issue 8 3801-3805, Copyright © 1995 by American Association of Immunologists

ARTICLES

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

S Kondo, B Wang, H Fujisawa, GM Shivji, B Echtenacher, TW Mak and DN Sauder
Division of Dermatology, Sunnybrook Health Science Centre, University of Toronto, Ontario, Canada.

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.

This article has been cited by other articles:

				B. Wang, C. Feliciani, I. Freed, Q. Cai, and D. N. Sauder Insights into molecular mechanisms of contact hypersensitivity gained from gene knockout studies J. Leukoc. Biol., August 1, 2001; 70(2): 185 - 191. [Abstract] [Full Text] [PDF]

				B. Wang, H. Fujisawa, L. Zhuang, I. Freed, B. G. Howell, S. Shahid, G. M. Shivji, T. W. Mak, and D. N. Sauder CD4+ Th1 and CD8+ Type 1 Cytotoxic T Cells Both Play a Crucial Role in the Full Development of Contact Hypersensitivity J. Immunol., December 15, 2000; 165(12): 6783 - 6790. [Abstract] [Full Text] [PDF]

				S. Ehlers, J. Benini, S. Kutsch, R. Endres, E. T. Rietschel, and K. Pfeffer Fatal Granuloma Necrosis without Exacerbated Mycobacterial Growth in Tumor Necrosis Factor Receptor p55 Gene-Deficient Mice Intravenously Infected with Mycobacterium avium Infect. Immun., July 1, 1999; 67(7): 3571 - 3579. [Abstract] [Full Text] [PDF]

				J. Kehren, C. Desvignes, M. Krasteva, M.-T. Ducluzeau, O. Assossou, F. Horand, M. Hahne, D. Kagi, D. Kaiserlian, and J.-F. Nicolas Cytotoxicity Is Mandatory for CD8+ T Cell-mediated Contact Hypersensitivity J. Exp. Med., March 1, 1999; 189(5): 779 - 786. [Abstract] [Full Text] [PDF]

				L. Zhuang, B. Wang, G. A. Shinder, G. M. Shivji, T. W. Mak, and D. N. Sauder TNF Receptor p55 Plays a Pivotal Role in Murine Keratinocyte Apoptosis Induced by Ultraviolet B Irradiation J. Immunol., February 1, 1999; 162(3): 1440 - 1447. [Abstract] [Full Text] [PDF]

				J. Hodge-Dufour, M. W. Marino, M. R. Horton, A. Jungbluth, M. D. Burdick, R. M. Strieter, P. W. Noble, C. A. Hunter, and E. Pure Inhibition of interferon gamma  induced interleukin 12 production: A potential mechanism for the anti-inflammatory activities of tumor necrosis factor PNAS, November 10, 1998; 95(23): 13806 - 13811. [Abstract] [Full Text] [PDF]

				M. W. Marino, A. Dunn, D. Grail, M. Inglese, Y. Noguchi, E. Richards, A. Jungbluth, H. Wada, M. Moore, B. Williamson, et al. Characterization of tumor necrosis factor-deficient mice PNAS, July 22, 1997; 94(15): 8093 - 8098. [Abstract] [Full Text] [PDF]