It has been believed that the Fas expressed on human peripheral blood T cells (PBT) is nonfunctional, because these cells are insensitive to agonistic anti-Fas/Apo-1 mAbs that efficiently kill in vitro–activated T cells and many Fas-expressing cell lines. Here, we demonstrate that membrane-bound Fas ligand (FasL) kills both fresh and in vitro–activated PBT, indicating that the Fas expressed on fresh PBT is functional. In contrast, soluble FasL kills only the latter. Naive T cells in umbilical cord blood do not express Fas, but can be induced to express Fas by IFN-γ or by a combination of IL-2 and anti-CD28 mAb, after which they acquire sensitivity to membrane but not to soluble FasL. Soluble FasL inhibited the killing of fresh PBT by membrane FasL. These results indicate that the shedding of FasL from the membrane is a mechanism for downregulating at least part of its killing activity.
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15 December 1997
Brief Definitive Report|
December 15 1997
Membrane Fas Ligand Kills Human Peripheral Blood T Lymphocytes, and Soluble Fas Ligand Blocks the Killing
Takashi Suda,
Takashi Suda
From the *Osaka Bioscience Institute, Department of Molecular Biology, Suita, Osaka 565, Japan; ‡Department of Orthopaedic Surgery, and §Department of Genetics, Osaka University Medical School Suita, Osaka 565, Japan
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Hideo Hashimoto,
Hideo Hashimoto
From the *Osaka Bioscience Institute, Department of Molecular Biology, Suita, Osaka 565, Japan; ‡Department of Orthopaedic Surgery, and §Department of Genetics, Osaka University Medical School Suita, Osaka 565, Japan
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Masato Tanaka,
Masato Tanaka
From the *Osaka Bioscience Institute, Department of Molecular Biology, Suita, Osaka 565, Japan; ‡Department of Orthopaedic Surgery, and §Department of Genetics, Osaka University Medical School Suita, Osaka 565, Japan
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Takahiro Ochi,
Takahiro Ochi
From the *Osaka Bioscience Institute, Department of Molecular Biology, Suita, Osaka 565, Japan; ‡Department of Orthopaedic Surgery, and §Department of Genetics, Osaka University Medical School Suita, Osaka 565, Japan
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Shigekazu Nagata
Shigekazu Nagata
From the *Osaka Bioscience Institute, Department of Molecular Biology, Suita, Osaka 565, Japan; ‡Department of Orthopaedic Surgery, and §Department of Genetics, Osaka University Medical School Suita, Osaka 565, Japan
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Takashi Suda
From the *Osaka Bioscience Institute, Department of Molecular Biology, Suita, Osaka 565, Japan; ‡Department of Orthopaedic Surgery, and §Department of Genetics, Osaka University Medical School Suita, Osaka 565, Japan
Hideo Hashimoto
From the *Osaka Bioscience Institute, Department of Molecular Biology, Suita, Osaka 565, Japan; ‡Department of Orthopaedic Surgery, and §Department of Genetics, Osaka University Medical School Suita, Osaka 565, Japan
Masato Tanaka
From the *Osaka Bioscience Institute, Department of Molecular Biology, Suita, Osaka 565, Japan; ‡Department of Orthopaedic Surgery, and §Department of Genetics, Osaka University Medical School Suita, Osaka 565, Japan
Takahiro Ochi
From the *Osaka Bioscience Institute, Department of Molecular Biology, Suita, Osaka 565, Japan; ‡Department of Orthopaedic Surgery, and §Department of Genetics, Osaka University Medical School Suita, Osaka 565, Japan
Shigekazu Nagata
From the *Osaka Bioscience Institute, Department of Molecular Biology, Suita, Osaka 565, Japan; ‡Department of Orthopaedic Surgery, and §Department of Genetics, Osaka University Medical School Suita, Osaka 565, Japan
Address correspondence to Takashi Suda, Osaka Bioscience Institute, Department of Molecular Biology, 6-2-4 Furuedai, Suita, Osaka 565, Japan. Phone: 81 6 872-4850; FAX: 81 6 871-6686; E-mail, [email protected]
The first two authors contributed equally to this manuscript.
Received:
July 28 1997
Revision Received:
October 15 1997
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1997
J Exp Med (1997) 186 (12): 2045–2050.
Article history
Received:
July 28 1997
Revision Received:
October 15 1997
Citation
Takashi Suda, Hideo Hashimoto, Masato Tanaka, Takahiro Ochi, Shigekazu Nagata; Membrane Fas Ligand Kills Human Peripheral Blood T Lymphocytes, and Soluble Fas Ligand Blocks the Killing . J Exp Med 15 December 1997; 186 (12): 2045–2050. doi: https://doi.org/10.1084/jem.186.12.2045
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