Expression and function of TNF-related apoptosis-inducing ligand on murine activated NK cells

Nobuhiko Kayagaki, Noriko Yamaguchi, Masafumi Nakayama, Kazuyoshi Takeda, Hisaya Akiba, Hiroko Tsutsui, Haruki Okamura, Kenji Nakanishi, Ko Okumura, Hideo Yagita

Research output: Contribution to journalArticlepeer-review

300 Citations (Scopus)


TNF-related apoptosis-inducing ligand (TRAIL), a new member of TNF family, induces apoptotic cell death of various tumor cells. We recently showed that TRAIL mediates perforin- and Fas ligand (FasL)-independent cytotoxic activity of human CD4+ T cell clones. In the present study, we investigated the expression and function of TRAIL on murine lymphocytes by using newly generated anti-murine TRAIL mAbs. Although freshly isolated T, B, or NK cells did not express a detectable level of TRAIL on their surface, a remarkable level of TRAIL expression was induced preferentially on CD3- NK1.1+ NK cells after stimulation with IL-2 or IL-15. In contrast, TRAIL expression was not induced by IL-18, whereas it efficiently potentiated lymphokine-activated killer activity of NK cells. In addition to perforin inactivation and neutralization of FasL by anti-FasL mAb, neutralization of TRAIL by anti-TRAIL mAb was needed for the complete inhibition of IL-2- or IL-15-activated NK cell cytotoxicity against mouse fibrosarcoma L929 target cells, which were susceptible to both FasL and TRAIL. These results indicated preferential expression of TRAIL on IL-2- or IL-15-activated NK cells and its potential involvement in lymphokine-activated killer activity.

Original languageEnglish
Pages (from-to)1906-1913
Number of pages8
JournalJournal of Immunology
Issue number4
Publication statusPublished - 1999 Aug 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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