Membrane Fas Ligand Kills Human Peripheral Blood T Lymphocytes, and Soluble Fas Ligand Blocks the Killing

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1998 Feb 12

PMID 9396774

Citations 115

Authors

T Suda

H Hashimoto

M Tanaka

T Ochi

S Nagata

Affiliations

Soon will be listed here.

Abstract

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-gamma 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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References

Kondo T, Suda T, Fukuyama H, Adachi M, Nagata S . Essential roles of the Fas ligand in the development of hepatitis. Nat Med. 1997; 3(4):409-13. DOI: 10.1038/nm0497-409. View

Fadeel B, Thorpe C, Yonehara S, Chiodi F . Anti-Fas IgG1 antibodies recognizing the same epitope of Fas/APO-1 mediate different biological effects in vitro. Int Immunol. 1997; 9(2):201-9. DOI: 10.1093/intimm/9.2.201. View

Yonehara S, Crump 3rd W, Grimm E . DNA fragmentation and cell death is selectively triggered in activated human lymphocytes by Fas antigen engagement. Cell Immunol. 1992; 140(1):197-205. DOI: 10.1016/0008-8749(92)90187-t. View

Miyawaki T, Uehara T, Nibu R, Tsuji T, Yachie A, Yonehara S . Differential expression of apoptosis-related Fas antigen on lymphocyte subpopulations in human peripheral blood. J Immunol. 1992; 149(11):3753-8. View

Ando K, Moriyama T, Guidotti L, Wirth S, Schreiber R, Schlicht H . Mechanisms of class I restricted immunopathology. A transgenic mouse model of fulminant hepatitis. J Exp Med. 1993; 178(5):1541-54. PMC: 2191233. DOI: 10.1084/jem.178.5.1541. View

Suda T, Takahashi T, Golstein P, Nagata S . Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell. 1993; 75(6):1169-78. DOI: 10.1016/0092-8674(93)90326-l. View

Wong G, Goeddel D . Fas antigen and p55 TNF receptor signal apoptosis through distinct pathways. J Immunol. 1994; 152(4):1751-5. View

Radinsky R, Kruzel E, Berry K, Yonehara S . Anti-Fas on nonhematopoietic tumors: levels of Fas/APO-1 and bcl-2 are not predictive of biological responsiveness. Cancer Res. 1994; 54(6):1580-6. View

Shima Y, Nishimoto N, Ogata A, Fujii Y, Yoshizaki K, Kishimoto T . Myeloma cells express Fas antigen/APO-1 (CD95) but only some are sensitive to anti-Fas antibody resulting in apoptosis. Blood. 1995; 85(3):757-64. View

10.

Nagata S, Suda T . Fas and Fas ligand: lpr and gld mutations. Immunol Today. 1995; 16(1):39-43. DOI: 10.1016/0167-5699(95)80069-7. View

11.

Tanaka M, Suda T, Takahashi T, Nagata S . Expression of the functional soluble form of human fas ligand in activated lymphocytes. EMBO J. 1995; 14(6):1129-35. PMC: 398190. DOI: 10.1002/j.1460-2075.1995.tb07096.x. View

12.

Nishimura Y, Ishii A, Kobayashi Y, Yamasaki Y, Yonehara S . Expression and function of mouse Fas antigen on immature and mature T cells. J Immunol. 1995; 154(9):4395-403. View

13.

Robertson M, Manley T, Pichert G, Cameron C, Cochran K, Levine H . Functional consequences of APO-1/Fas (CD95) antigen expression by normal and neoplastic hematopoietic cells. Leuk Lymphoma. 1995; 17(1-2):51-61. DOI: 10.3109/10428199509051703. View

14.

Bellgrau D, Gold D, Selawry H, Moore J, Franzusoff A, Duke R . A role for CD95 ligand in preventing graft rejection. Nature. 1995; 377(6550):630-2. DOI: 10.1038/377630a0. View

15.

Griffith T, Brunner T, Fletcher S, Green D, Ferguson T . Fas ligand-induced apoptosis as a mechanism of immune privilege. Science. 1995; 270(5239):1189-92. DOI: 10.1126/science.270.5239.1189. View

16.

Kayagaki N, Kawasaki A, Ebata T, Ohmoto H, Ikeda S, Inoue S . Metalloproteinase-mediated release of human Fas ligand. J Exp Med. 1995; 182(6):1777-83. PMC: 2192231. DOI: 10.1084/jem.182.6.1777. View

17.

Grell M, Douni E, Wajant H, Lohden M, Clauss M, Maxeiner B . The transmembrane form of tumor necrosis factor is the prime activating ligand of the 80 kDa tumor necrosis factor receptor. Cell. 1995; 83(5):793-802. DOI: 10.1016/0092-8674(95)90192-2. View

18.

Braun M, Lowin B, French L, Acha-Orbea H, Tschopp J . Cytotoxic T cells deficient in both functional fas ligand and perforin show residual cytolytic activity yet lose their capacity to induce lethal acute graft-versus-host disease. J Exp Med. 1996; 183(2):657-61. PMC: 2192472. DOI: 10.1084/jem.183.2.657. View

19.

Tanaka M, Suda T, Haze K, Nakamura N, Sato K, Kimura F . Fas ligand in human serum. Nat Med. 1996; 2(3):317-22. DOI: 10.1038/nm0396-317. View

20.

Fujisawa K, Asahara H, Okamoto K, Aono H, Hasunuma T, Kobata T . Therapeutic effect of the anti-Fas antibody on arthritis in HTLV-1 tax transgenic mice. J Clin Invest. 1996; 98(2):271-8. PMC: 507427. DOI: 10.1172/JCI118789. View