Involvement of TWEAK in Interferon {gamma}-stimulated Monocyte Cytotoxicity

doi:10.1084/jem.192.9.1373

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Published online 6 November 2000.

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© The Rockefeller University Press, 0022-1007/2000/11/1373/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 9, November 6, 2000 1373-1380

Brief Definitive Reports

Involvement of TWEAK in Interferon ${gamma}$ –stimulated Monocyte Cytotoxicity

Masafumi Nakayama^a,b, Nobuhiko Kayagaki^a,c, Noriko Yamaguchi^a,c, Ko Okumura^a,c, and Hideo Yagita^a,c
^a Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
^b Allergy Research Center, Juntendo University School of Medicine, Tokyo 113-8421, Japan
^c Core Research for Evolutional Science and Technology of Japan Science and Technology Corporation, Tokyo 101-0062, Japan

Correspondence to: Hideo Yagita, Dept. of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Tel:81-3-3818-9284 Fax:81-3-3813-0421

TWEAK, a new member of the tumor necrosis factor (TNF) family,induces cell death in some tumor cell lines, but its physiologicalfunctions are largely unknown. In this study, we investigatedthe expression and function of TWEAK in human peripheral bloodmononuclear cells (PBMCs) by using newly generated anti–humanTWEAK mAbs. Although freshly isolated PBMCs expressed no detectablelevel of TWEAK on their surfaces, a remarkable TWEAK expressionwas rapidly observed on monocytes upon stimulation with interferon(IFN)- ${gamma}$ but not with IFN- ${alpha}$ or lipopolysaccharide. Cytotoxic activityof IFN- ${gamma}$ –stimulated monocytes against human squamous carcinomacell line HSC3 was inhibited partially by anti-TWEAK mAb aloneand almost completely by combination with anti-TRAIL (TNF-relatedapoptosis-inducing ligand) mAb. These results revealed a novelpathway of monocyte cytotoxicity against tumor cells that ismediated by TWEAK and potentiated by IFN- ${gamma}$ .

Key Words: TWEAK, TRAIL, IFN- ${gamma}$ , monocyte, cytotoxicity

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Brief Definitive Reports

Involvement of TWEAK in Interferon –stimulated Monocyte Cytotoxicity

Involvement of TWEAK in Interferon ${gamma}$ –stimulated Monocyte Cytotoxicity