J. Exp. Med., Volume 188, Number 5, September 7, 1998 887-896

Antiinflammatory Effects of CD95 Ligand (FasL)-induced Apoptosis

By Yakun Gao, John M. Herndon, Hui Zhang, Thomas S. Griffith, and Thomas A. Ferguson

From the Department of Ophthalmology and Visual Sciences and the Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110

Apoptosis is critical to homeostasis of multicellular organisms. In immune privileged sites such as the eye, CD95 ligand (FasL)-induced apoptosis controls dangerous inflammatory reactions that can cause blindness. Recently, we demonstrated that apoptotic cell death of inflammatory cells was a prerequisite for the induction of immune deviation after antigen presentation in the eye. In this report, we examine the mechanism by which this takes place. Our results show that Fas- mediated apoptosis of lymphoid cells leads to rapid production of interleukin (IL)-10 in these cells. The apoptotic cells containing IL-10 are responsible for the activation of immune deviation through interaction with antigen-presenting cells (APC). In support of this, we found that apoptotic cells from IL-10^+/+ animals fed to APC in vitro promote Th2 cell differentiation, whereas apoptotic IL-10^/ cells, as well as nonapoptotic cells, favor Th1 induction. Thus, apoptotic cell death and tolerance are linked through the production of an antiinflammatory cytokine to prevent dangerous and unwanted immune responses that might compromise organ integrity.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Griffith, T. S., Kazama, H., VanOosten, R. L., Earle, J. K. Jr., Herndon, J. M., Green, D. R., Ferguson, T. A. (2007). Apoptotic Cells Induce Tolerance by Generating Helpless CD8+ T Cells That Produce TRAIL. J. Immunol. 178: 2679-2687 [Abstract] [Full Text]  
• Greenberg, M. E., Sun, M., Zhang, R., Febbraio, M., Silverstein, R., Hazen, S. L. (2006). Oxidized phosphatidylserine-CD36 interactions play an essential role in macrophage-dependent phagocytosis of apoptotic cells. J. Exp. Med. 203: 2613-2625 [Abstract] [Full Text]  
• Rowe, V., Banovic, T., MacDonald, K. P., Kuns, R., Don, A. L., Morris, E. S., Burman, A. C., Bofinger, H. M., Clouston, A. D., Hill, G. R. (2006). Host B cells produce IL-10 following TBI and attenuate acute GVHD after allogeneic bone marrow transplantation. Blood 108: 2485-2492 [Abstract] [Full Text]  
• Daryadel, A., Grifone, R. F., Simon, H.-U., Yousefi, S. (2006). Apoptotic Neutrophils Release Macrophage Migration Inhibitory Factor upon Stimulation with Tumor Necrosis Factor-{alpha}. J. Biol. Chem. 281: 27653-27661 [Abstract] [Full Text]  
• Nowak, M., Kopp, F., Roelofs-Haarhuis, K., Wu, X., Gleichmann, E. (2006). Oral nickel tolerance: fas ligand-expressing invariant NK T cells promote tolerance induction by eliciting apoptotic death of antigen-carrying, effete B cells.. J. Immunol. 176: 4581-4589 [Abstract] [Full Text]  
• Tedgui, A., Mallat, Z. (2006). Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways. Physiol. Rev. 86: 515-581 [Abstract] [Full Text]  
• Vacchio, M. S., Hodes, R. J. (2005). Fetal Expression of Fas Ligand Is Necessary and Sufficient for Induction of CD8 T Cell Tolerance to the Fetal Antigen H-Y during Pregnancy. J. Immunol. 174: 4657-4661 [Abstract] [Full Text]  
• Herndon, J. M., Stuart, P. M., Ferguson, T. A. (2005). Peripheral Deletion of Antigen-Specific T Cells Leads to Long-Term Tolerance Mediated by CD8+ Cytotoxic Cells. J. Immunol. 174: 4098-4104 [Abstract] [Full Text]  
• Bohana-Kashtan, O., Civin, C. I. (2004). Fas Ligand as a Tool for Immunosuppression and Generation of Immune Tolerance. Stem Cells 22: 908-924 [Abstract] [Full Text]  
• Niederkorn, J. Y., Mayhew, E., Mellon, J., Hegde, S. (2004). Role of Tumor Necrosis Factor Receptor Expression in Anterior Chamber-Associated Immune Deviation (ACAID) and Corneal Allograft Survival. IOVS 45: 2674-2681 [Abstract] [Full Text]  
• Chen, K., Wei, Y., Sharp, G. C., Braley-Mullen, H. (2003). Mechanisms of Spontaneous Resolution versus Fibrosis in Granulomatous Experimental Autoimmune Thyroiditis. J. Immunol. 171: 6236-6243 [Abstract] [Full Text]  
• Yang, B.-C., Lin, H.-K., Hor, W.-S., Hwang, J.-Y., Lin, Y.-P., Liu, M.-Y., Wang, Y.-J. (2003). Mediation of Enhanced Transcription of the IL-10 Gene in T Cells, Upon Contact with Human Glioma Cells, by Fas Signaling Through a Protein Kinase A-Independent Pathway. J. Immunol. 171: 3947-3954 [Abstract] [Full Text]  
• Elhalel, M. D., Huang, J.-H., Schmidt, W., Rachmilewitz, J., Tykocinski, M. L. (2003). CTLA-4 {middle dot} FasL Induces Alloantigen-Specific Hyporesponsiveness. J. Immunol. 170: 5842-5850 [Abstract] [Full Text]  
• Olivieri, A., De Angelis, S., Vaccari, V., Valensise, H., Magnani, F., Stazi, M. A., Cotichini, R., Gilardi, E., Cordeddu, V., Sorcini, M., Boirivant, M. (2003). Postpartum Thyroiditis Is Associated with Fluctuations in Transforming Growth Factor-{beta}1 Serum Levels. J. Clin. Endocrinol. Metab. 88: 1280-1284 [Abstract] [Full Text]  
• Hor, W.-S., Huang, W.-L., Lin, Y.-S., Yang, B.-C. (2003). Cross-talk between tumor cells and neutrophils through the Fas (APO-1, CD95)/FasL system: human glioma cells enhance cell viability and stimulate cytokine production in neutrophils. J. Leukoc. Biol. 73: 363-368 [Abstract] [Full Text]  
• Schonbeck, U., Sukhova, G. K., Gerdes, N., Libby, P. (2002). TH2 Predominant Immune Responses Prevail in Human Abdominal Aortic Aneurysm. Am. J. Pathol. 161: 499-506 [Abstract] [Full Text]  
• Ferguson, T. A., Herndon, J., Elzey, B., Griffith, T. S., Schoenberger, S., Green, D. R. (2002). Uptake of Apoptotic Antigen-Coupled Cells by Lymphoid Dendritic Cells and Cross-Priming of CD8+ T Cells Produce Active Immune Unresponsiveness. J. Immunol. 168: 5589-5595 [Abstract] [Full Text]  
• Liversidge, J., Dick, A., Gordon, S. (2002). Nitric Oxide Mediates Apoptosis Through Formation of Peroxynitrite and Fas/Fas-Ligand Interactions in Experimental Autoimmune Uveitis. Am. J. Pathol. 160: 905-916 [Abstract] [Full Text]  
• Byrne, A., Reen, D. J. (2002). Lipopolysaccharide Induces Rapid Production of IL-10 by Monocytes in the Presence of Apoptotic Neutrophils. J. Immunol. 168: 1968-1977 [Abstract] [Full Text]  
• Tzachanis, D., Berezovskaya, A., Nadler, L. M., Boussiotis, V. A. (2002). Blockade of B7/CD28 in mixed lymphocyte reaction cultures results in the generation of alternatively activated macrophages, which suppress T-cell responses. Blood 99: 1465-1473 [Abstract] [Full Text]  
• McKechnie, N. M., Gurr, W., Yamada, H., Copland, D., Braun, G. (2002). Antigenic Mimicry: Onchocerca volvulus Antigen-Specific T Cells and Ocular Inflammation. IOVS 43: 411-418 [Abstract] [Full Text]  
• Lipscomb, M. F., Masten, B. J. (2002). Dendritic Cells: Immune Regulators in Health and Disease. Physiol. Rev. 82: 97-130 [Abstract] [Full Text]  
• Kammerer, R., Stober, D., Riedl, P., Oehninger, C., Schirmbeck, R., Reimann, J. (2002). Noncovalent Association with Stress Protein Facilitates Cross-Priming of CD8+ T Cells to Tumor Cell Antigens by Dendritic Cells. J. Immunol. 168: 108-117 [Abstract] [Full Text]  
• Elzey, B. D., Griffith, T. S., Herndon, J. M., Barreiro, R., Tschopp, J., Ferguson, T. A. (2001). Regulation of Fas Ligand-Induced Apoptosis by TNF. J. Immunol. 167: 3049-3056 [Abstract] [Full Text]  
• Bittencourt, M. d. C., Perruche, S., Contassot, E., Fresnay, S., Baron, M.-H., Angonin, R., Aubin, F., Herve, P., Tiberghien, P., Saas, P. (2001). Intravenous injection of apoptotic leukocytes enhances bone marrow engraftment across major histocompatibility barriers. Blood 98: 224-230 [Abstract] [Full Text]  
• Daniel, C., Duffield, J., Brunner, T., Steinmann-Niggli, K., Lods, N., Marti, H.-P. (2001). Matrix Metalloproteinase Inhibitors Cause Cell Cycle Arrest and Apoptosis in Glomerular Mesangial Cells. J. Pharmacol. Exp. Ther. 297: 57-68 [Abstract] [Full Text]  
• Roozendaal, R., Vellenga, E., de Jong, M. A., Traanberg, K. F., Postma, D. S., de Monchy, J. G. R., Kauffman, H. F. (2001). Resistance of activated human Th2 cells to NO-induced apoptosis is mediated by {{gamma}}-glutamyltranspeptidase. Int Immunol 13: 519-528 [Abstract] [Full Text]  
• Sandri, M., Sandri, C., Brun, B., Giurisato, E., Cantini, M., Rossini, K., Destro, C., Arslan, P., Carraro, U. (2001). Inhibition of FasL sustains phagocytic cells and delays myogenesis in regenerating muscle fibers. J. Leukoc. Biol. 69: 482-489 [Abstract] [Full Text]  
• Sonoda, K.-H., Faunce, D. E., Taniguchi, M., Exley, M., Balk, S., Stein-Streilein, J. (2001). NK T Cell-Derived IL-10 Is Essential for the Differentiation of Antigen-Specific T Regulatory Cells in Systemic Tolerance. J. Immunol. 166: 42-50 [Abstract] [Full Text]  
• Paul, A. G. A., van Kooten, P. J. S., van Eden, W., van der Zee, R. (2000). Highly Autoproliferative T Cells Specific for 60-kDa Heat Shock Protein Produce IL-4/IL-10 and IFN-{gamma} and Are Protective in Adjuvant Arthritis. J. Immunol. 165: 7270-7277 [Abstract] [Full Text]  
• Jean, M. D. S., Debbasch, C., Rahmani, M., Brignole, F., Feldmann, G., Warnet, J.-M., Baudouin, C. (2000). Fas- and Interferon {gamma}-Induced Apoptosis in Chang Conjunctival Cells: Further Investigations. IOVS 41: 2531-2543 [Abstract] [Full Text]  
• Broderick, C., Duncan, L., Taylor, N., Dick, A. D. (2000). IFN-{gamma} and LPS-Mediated IL-10-Dependent Suppression of Retinal Microglial Activation. IOVS 41: 2613-2622 [Abstract] [Full Text]  
• Wittig, B. M., Johansson, B., Zoller, M., Schwarzler, C., Gunthert, U. (2000). Abrogation of Experimental Colitis Correlates with Increased Apoptosis in Mice Deficient for CD44 Variant Exon 7 (CD44v7). J. Exp. Med. 191: 2053-2064 [Abstract] [Full Text]  
• Yano, M., Kishida, E., Iwasaki, M., Kojo, S., Masuzawa, Y. (2000). Docosahexaenoic Acid and Vitamin E Can Reduce Human Monocytic U937 Cell Apoptosis Induced by Tumor Necrosis Factor. J. Nutr. 130: 1095-1101 [Abstract] [Full Text]  
• Hohlbaum, A. M., Moe, S., Marshak-Rothstein, A. (2000). Opposing Effects of Transmembrane and Soluble Fas Ligand Expression on Inflammation and Tumor Cell Survival. J. Exp. Med. 191: 1209-1220 [Abstract] [Full Text]  
• Pinkoski, M. J., Brunner, T., Green, D. R., Lin, T. (2000). Fas and Fas ligand in gut and liver. Am. J. Physiol. Gastrointest. Liver Physiol. 278: G354-G366 [Abstract] [Full Text]  
• Sauter, B., Albert, M. L., Francisco, L., Larsson, M., Somersan, S., Bhardwaj, N. (2000). Consequences of Cell Death: Exposure to Necrotic Tumor Cells, but Not Primary Tissue Cells or Apoptotic Cells, Induces the Maturation of Immunostimulatory Dendritic Cells. J. Exp. Med. 191: 423-434 [Abstract] [Full Text]  
• Hong, S., Van Kaer, L. (1999). Immune Privilege: Keeping an Eye on Natural Killer T Cells. J. Exp. Med. 190: 1197-1200 [Full Text]  
• Sonoda, K.-H., Exley, M., Snapper, S., Balk, S. P., Stein-Streilein, J. (1999). CD1-reactive Natural Killer T Cells Are Required for Development of Systemic Tolerance through an Immune-Privileged Site. J. Exp. Med. 190: 1215-1226 [Abstract] [Full Text]  
• de Carvalho Bittencourt, M., Tiberghien, P., Saas, P., Gallardo, D., Granena, A., Garcia-Lopez, J. (1999). Transplantation of Anergic Histoincompatible Bone Marrow Cells. NEJM 341: 1081-1082 [Full Text]  
• Dick, A. D., Siepmann, K., Dees, C., Duncan, L., Broderick, C., Liversidge, J., Forrester, J. V. (1999). Fas-Fas Ligand-Mediated Apoptosis within Aqueous during Idiopathic Acute Anterior Uveitis. IOVS 40: 2258-2267 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS