Involvement of TNF-related apoptosis-inducing ligand in human CD4+ T cell-mediated cytotoxicity

Nobuhiko Kayagaki, Noriko Yamaguchi, Masafumi Nakayama, Akemi Kawasaki, Hisaya Akiba, Ko Okumura, Hideo Yagita

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211 Citations (Scopus)

Abstract

TNF-related apoptosis-inducing ligand (TRAIL) has been identified as a member of the TNF family that induces apoptosis in a variety of tumor cells, but its physiological functions are largely unknown. In the present study, we examined the expression and function of TRAIL in human CD4+ T cell clones by utilizing newly established anti-human TRAIL mAbs. Human CD4+ T cell clones, HK12 and 4HM1, exhibited perforin-independent and Fas ligand (FasL)- independent cytotoxicity against certain target cells, including T lymphoma (Jurkat) and keratinocyte (HaCaT) cell lines, which are susceptible to TRAIL- mediated cytotoxicity. In contrast to FasL, the expression of which was inducible upon anti-CD3 stimulation, TRAIL was constitutively expressed on HK12 and 4HM1 cells, and no further increase was observed after anti-CD3 stimulation. Spontaneous cytotoxic activities of resting HK12 and 4HM1 cells against Jurkat and HaCaT cells were blocked by anti-TRAIL mAb but not by anti-FasL mAb, and bystander cytotoxic activities of anti-CD3-stimulated HK12 and 4HM1 cells were abolished by the combination of anti-TRAIL and anti-FasL mAbs. These results indicate a differential regulation of TRAIL and FasL expression on human CD4+ T cell clones and that TRAIL constitutes an additional pathway of T cell-mediated cytotoxicity.

Original languageEnglish
Pages (from-to)2639-2647
Number of pages9
JournalJournal of Immunology
Volume162
Issue number5
Publication statusPublished - 1999 Mar 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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