J. Exp. Med., Volume 186, Number 12, December 15, 1997 2045-2050

BRIEF DEFINITIVE REPORT:
Membrane Fas Ligand Kills Human Peripheral Blood T Lymphocytes, and Soluble Fas Ligand Blocks the Killing

By Takashi Suda,^* Hideo Hashimoto,^* Masato Tanaka,^§ Takahiro Ochi, and 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

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- 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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