Abstract
AIMS: To confirm the recent data obtained in mice, showing that the Fas ligand (FasL) is involved in the phenomenon of "immune privilege" (the apparent defect of the immune system in specific anatomical sites) and to extend this finding to humans. METHODS: The expression of FasL was analysed in a panel of histologically normal human tissues by reverse transcriptase polymerase chain reaction and Western blotting. The tissues sampled were brain, breast, bone marrow, oesophagus, kidney, liver, lung, lymph node, ovary, pancreas, pituitary gland, prostate, spleen, stomach (antrum and fundus), striated muscle, testis, thyroid, and uterus. These were obtained from patients with various neoplastic and non-neoplastic disorders; placental tissue was obtained after normal obstetric delivery, and spontaneous or voluntary abortion. RESULTS: Strong FasL expression was detected in testis and placenta. FasL expression was also detectable, although it was seen to a lesser extent, in oesophagus, prostate, lung, and uterus, which also coexpressed variable amounts of Fas mRNA or protein or both. The other organs tested for FasL expression were all negative. CONCLUSIONS: FasL in humans is expressed predominantly in immune "sanctuaries" such as testis and placenta, suggesting that, similar to mice, this expression may contribute to the immune privileged status of these organs, by preventing dangerous inflammatory responses. The coexpression of FasL and Fas in particular epithelia suggests that the physiological cell turnover of some tissues may be regulated by the Fas-FasL apoptotic pathway.
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- Alderson M. R., Tough T. W., Davis-Smith T., Braddy S., Falk B., Schooley K. A., Goodwin R. G., Smith C. A., Ramsdell F., Lynch D. H. Fas ligand mediates activation-induced cell death in human T lymphocytes. J Exp Med. 1995 Jan 1;181(1):71–77. doi: 10.1084/jem.181.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Armitage R. J. Tumor necrosis factor receptor superfamily members and their ligands. Curr Opin Immunol. 1994 Jun;6(3):407–413. doi: 10.1016/0952-7915(94)90119-8. [DOI] [PubMed] [Google Scholar]
- Bellgrau D., Gold D., Selawry H., Moore J., Franzusoff A., Duke R. C. A role for CD95 ligand in preventing graft rejection. Nature. 1995 Oct 19;377(6550):630–632. doi: 10.1038/377630a0. [DOI] [PubMed] [Google Scholar]
- Chu J. L., Ramos P., Rosendorff A., Nikolić-Zugić J., Lacy E., Matsuzawa A., Elkon K. B. Massive upregulation of the Fas ligand in lpr and gld mice: implications for Fas regulation and the graft-versus-host disease-like wasting syndrome. J Exp Med. 1995 Jan 1;181(1):393–398. doi: 10.1084/jem.181.1.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Debatin K. M., Goldman C. K., Waldmann T. A., Krammer P. H. APO-1-induced apoptosis of leukemia cells from patients with adult T-cell leukemia. Blood. 1993 Jun 1;81(11):2972–2977. [PubMed] [Google Scholar]
- Debatin K. M., Goldmann C. K., Bamford R., Waldmann T. A., Krammer P. H. Monoclonal-antibody-mediated apoptosis in adult T-cell leukaemia. Lancet. 1990 Mar 3;335(8688):497–500. doi: 10.1016/0140-6736(90)90735-n. [DOI] [PubMed] [Google Scholar]
- Fisher G. H., Rosenberg F. J., Straus S. E., Dale J. K., Middleton L. A., Lin A. Y., Strober W., Lenardo M. J., Puck J. M. Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell. 1995 Jun 16;81(6):935–946. doi: 10.1016/0092-8674(95)90013-6. [DOI] [PubMed] [Google Scholar]
- French L. E., Hahne M., Viard I., Radlgruber G., Zanone R., Becker K., Müller C., Tschopp J. Fas and Fas ligand in embryos and adult mice: ligand expression in several immune-privileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover. J Cell Biol. 1996 Apr;133(2):335–343. doi: 10.1083/jcb.133.2.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Itoh N., Yonehara S., Ishii A., Yonehara M., Mizushima S., Sameshima M., Hase A., Seto Y., Nagata S. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 1991 Jul 26;66(2):233–243. doi: 10.1016/0092-8674(91)90614-5. [DOI] [PubMed] [Google Scholar]
- Leithäuser F., Dhein J., Mechtersheimer G., Koretz K., Brüderlein S., Henne C., Schmidt A., Debatin K. M., Krammer P. H., Möller P. Constitutive and induced expression of APO-1, a new member of the nerve growth factor/tumor necrosis factor receptor superfamily, in normal and neoplastic cells. Lab Invest. 1993 Oct;69(4):415–429. [PubMed] [Google Scholar]
- Lynch D. H., Watson M. L., Alderson M. R., Baum P. R., Miller R. E., Tough T., Gibson M., Davis-Smith T., Smith C. A., Hunter K. The mouse Fas-ligand gene is mutated in gld mice and is part of a TNF family gene cluster. Immunity. 1994 May;1(2):131–136. doi: 10.1016/1074-7613(94)90106-6. [DOI] [PubMed] [Google Scholar]
- Möller P., Henne C., Leithäuser F., Eichelmann A., Schmidt A., Brüderlein S., Dhein J., Krammer P. H. Coregulation of the APO-1 antigen with intercellular adhesion molecule-1 (CD54) in tonsillar B cells and coordinate expression in follicular center B cells and in follicle center and mediastinal B-cell lymphomas. Blood. 1993 Apr 15;81(8):2067–2075. [PubMed] [Google Scholar]
- Nagata S., Golstein P. The Fas death factor. Science. 1995 Mar 10;267(5203):1449–1456. doi: 10.1126/science.7533326. [DOI] [PubMed] [Google Scholar]
- Oehm A., Behrmann I., Falk W., Pawlita M., Maier G., Klas C., Li-Weber M., Richards S., Dhein J., Trauth B. C. Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily. Sequence identity with the Fas antigen. J Biol Chem. 1992 May 25;267(15):10709–10715. [PubMed] [Google Scholar]
- Owen-Schaub L. B., Meterissian S., Ford R. J. Fas/APO-1 expression and function on malignant cells of hematologic and nonhematologic origin. J Immunother Emphasis Tumor Immunol. 1993 Oct;14(3):234–241. doi: 10.1097/00002371-199310000-00011. [DOI] [PubMed] [Google Scholar]
- Ramsdell F., Seaman M. S., Miller R. E., Tough T. W., Alderson M. R., Lynch D. H. gld/gld mice are unable to express a functional ligand for Fas. Eur J Immunol. 1994 Apr;24(4):928–933. doi: 10.1002/eji.1830240422. [DOI] [PubMed] [Google Scholar]
- Rieux-Laucat F., Le Deist F., Hivroz C., Roberts I. A., Debatin K. M., Fischer A., de Villartay J. P. Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity. Science. 1995 Jun 2;268(5215):1347–1349. doi: 10.1126/science.7539157. [DOI] [PubMed] [Google Scholar]
- Schulze-Osthoff K. The Fas/APO-1 receptor and its deadly ligand. Trends Cell Biol. 1994 Dec;4(12):421–426. doi: 10.1016/0962-8924(94)90102-3. [DOI] [PubMed] [Google Scholar]
- Selawry H. P., Whittington K. B., Bellgrau D. Abdominal intratesticular islet-xenograft survival in rats. Diabetes. 1989 Jan;38 (Suppl 1):220–223. doi: 10.2337/diab.38.1.s220. [DOI] [PubMed] [Google Scholar]
- Steller H. Mechanisms and genes of cellular suicide. Science. 1995 Mar 10;267(5203):1445–1449. doi: 10.1126/science.7878463. [DOI] [PubMed] [Google Scholar]
- Strasser A. Apoptosis. Death of a T cell. Nature. 1995 Feb 2;373(6513):385–386. doi: 10.1038/373385a0. [DOI] [PubMed] [Google Scholar]
- Suda T., Nagata S. Purification and characterization of the Fas-ligand that induces apoptosis. J Exp Med. 1994 Mar 1;179(3):873–879. doi: 10.1084/jem.179.3.873. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Suda T., Okazaki T., Naito Y., Yokota T., Arai N., Ozaki S., Nakao K., Nagata S. Expression of the Fas ligand in cells of T cell lineage. J Immunol. 1995 Apr 15;154(8):3806–3813. [PubMed] [Google Scholar]
- 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 Dec 17;75(6):1169–1178. doi: 10.1016/0092-8674(93)90326-l. [DOI] [PubMed] [Google Scholar]
- Suzuki A., Enari M., Eguchi Y., Matsuzawa A., Nagata S., Tsujimoto Y., Iguchi T. Involvement of Fas in regression of vaginal epithelia after ovariectomy and during an estrous cycle. EMBO J. 1996 Jan 15;15(2):211–215. [PMC free article] [PubMed] [Google Scholar]
- Takahashi T., Tanaka M., Brannan C. I., Jenkins N. A., Copeland N. G., Suda T., Nagata S. Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell. 1994 Mar 25;76(6):969–976. doi: 10.1016/0092-8674(94)90375-1. [DOI] [PubMed] [Google Scholar]
- Takahashi T., Tanaka M., Inazawa J., Abe T., Suda T., Nagata S. Human Fas ligand: gene structure, chromosomal location and species specificity. Int Immunol. 1994 Oct;6(10):1567–1574. doi: 10.1093/intimm/6.10.1567. [DOI] [PubMed] [Google Scholar]
- Tanaka M., Suda T., Takahashi T., Nagata S. Expression of the functional soluble form of human fas ligand in activated lymphocytes. EMBO J. 1995 Mar 15;14(6):1129–1135. doi: 10.1002/j.1460-2075.1995.tb07096.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Watanabe-Fukunaga R., Brannan C. I., Copeland N. G., Jenkins N. A., Nagata S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992 Mar 26;356(6367):314–317. doi: 10.1038/356314a0. [DOI] [PubMed] [Google Scholar]
- Xerri L., Carbuccia N., Parc P., Hassoun J., Birg F. Frequent expression of FAS/APO-1 in Hodgkin's disease and anaplastic large cell lymphomas. Histopathology. 1995 Sep;27(3):235–241. doi: 10.1111/j.1365-2559.1995.tb00215.x. [DOI] [PubMed] [Google Scholar]
- Xerri L., Mathoulin M. P., Birg F., Bouabdallah R., Stoppa A. M., Hassoun J. Heterogeneity of rearranged T-cell receptor V-alpha and V-beta transcripts in tumor-infiltrating lymphocytes from Hodgkin's disease and non-Hodgkin's lymphoma. Am J Clin Pathol. 1994 Jan;101(1):76–80. doi: 10.1093/ajcp/101.1.76. [DOI] [PubMed] [Google Scholar]