Massive upregulation of the Fas ligand in lpr and gld mice: implications for Fas regulation and the graft-versus-host disease-like wasting syndrome

doi:10.1084/jem.181.1.393

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Massive upregulation of the Fas ligand in lpr and gld mice: implications for Fas regulation and the graft-versus-host disease-like wasting syndrome

JL Chu, P Ramos, A Rosendorff, J Nikolic-Zugic, E Lacy, A Matsuzawa and KB Elkon
Specialized Center of Research in Systemic Lupus Erythematosus, Hospital for Special Surgery-Cornell University Medical Center, New York 10021.

Fas-deficient lpr and gld mice develop lymphadenopathy due to the accumulation of T cells with an unusual double negative (DN) (CD4-CD8-) phenotype. Previous studies have shown that these abnormal cells are capable of inducing redirected lysis of certain Fc receptor-positive target cells. Since the Fas ligand (FasL) has recently been shown to be partly responsible for T cell-mediated cytotoxicity, lymph node cells from lpr and gld mice were examined for the expression of FasL mRNA. Northern blot analysis revealed that lymph node cells obtained from lpr and gld mice had a striking increase in the level of expression of FasL mRNA predominantly due to expression in the DN T cells. Furthermore, lpr, but not gld lymph node cells killed the B cell line, A20, in a Fas- dependent manner. These findings indicate that Fas mutations result in a massive up-regulation of FasL which, most likely, results from repetitive exposure to (self) antigen. This phenomenon could explain the lpr-induced wasting syndrome observed when lpr bone marrow-derived cells are adoptively transferred to wild-type recipients.
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Bonardelle, D., Benihoud, K., Kiger, N., Bobe, P. (2005). B lymphocytes mediate Fas-dependent cytotoxicity in MRL/lpr mice. J. Leukoc. Biol. 78: 1052-1059 [Abstract] [Full Text]
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Yajima, N., Sakamaki, K., Yonehara, S. (2004). Age-related thymic involution is mediated by Fas on thymic epithelial cells. Int Immunol 16: 1027-1035 [Abstract] [Full Text]
Hao, Z., Hampel, B., Yagita, H., Rajewsky, K. (2004). T Cell-specific Ablation of Fas Leads to Fas Ligand-mediated Lymphocyte Depletion and Inflammatory Pulmonary Fibrosis. JEM 199: 1355-1365 [Abstract] [Full Text]
Xiao, S., Zhang, X., Mann, K. K., Jodo, S., Li, L., Jarjour, W. N., Marshak-Rothstein, A., Sherr, D. H., Ju, S.-T. (2004). Changes in sensitivity of peripheral lymphocytes of autoimmune gld mice to FasL-mediated apoptosis reveal a mechanism for the preferential deletion of CD4-CD8-B220+ T cells. Int Immunol 16: 759-766 [Abstract] [Full Text]
Roth, E., Pircher, H. (2004). IFN-{gamma} Promotes Fas Ligand- and Perforin-Mediated Liver Cell Destruction by Cytotoxic CD8 T Cells. J. Immunol. 172: 1588-1594 [Abstract] [Full Text]
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Savinov, A. Y., Tcherepanov, A., Green, E. A., Flavell, R. A., Chervonsky, A. V. (2003). Contribution of Fas to diabetes development. Proc. Natl. Acad. Sci. USA 100: 628-632 [Abstract] [Full Text]
Kennedy, N. J., Russell, J. Q., Michail, N., Budd, R. C. (2001). Liver Damage by Infiltrating CD8+ T Cells Is Fas Dependent. J. Immunol. 167: 6654-6662 [Abstract] [Full Text]
Ishimaru, N., Yanagi, K., Ogawa, K., Suda, T., Saito, I., Hayashi, Y. (2001). Possible Role of Organ-Specific Autoantigen for Fas Ligand-Mediated Activation-Induced Cell Death in Murine Sjogren's Syndrome. J. Immunol. 167: 6031-6037 [Abstract] [Full Text]
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Wahlsten, J. L., Gitchell, H. L., Chan, C.-C., Wiggert, B., Caspi, R. R. (2000). Fas and Fas Ligand Expressed on Cells of the Immune System, not on the Target Tissue, Control Induction of Experimental Autoimmune Uveitis. J. Immunol. 165: 5480-5486 [Abstract] [Full Text]
Suzuki, I., Martin, S., Boursalian, T. E., Beers, C., Fink, P. J. (2000). Fas Ligand Costimulates the In Vivo Proliferation of CD8+ T Cells. J. Immunol. 165: 5537-5543 [Abstract] [Full Text]
Teh, H.-S., Seebaran, A., Teh, S.-J. (2000). TNF Receptor 2-Deficient CD8 T Cells Are Resistant to Fas/Fas Ligand-Induced Cell Death. J. Immunol. 165: 4814-4821 [Abstract] [Full Text]
Kim, S., Kim, K.-A., Hwang, D.-Y., Lee, T. H., Kayagaki, N., Yagita, H., Lee, M.-S. (2000). Inhibition of Autoimmune Diabetes by Fas Ligand: The Paradox Is Solved. J. Immunol. 164: 2931-2936 [Abstract] [Full Text]
Su, X., Hu, Q., Kristan, J. M., Costa, C., Shen, Y., Gero, D., Matis, L. A., Wang, Y. (2000). Significant Role for Fas in the Pathogenesis of Autoimmune Diabetes. J. Immunol. 164: 2523-2532 [Abstract] [Full Text]
Suzuki, I., Fink, P. J. (2000). The dual functions of Fas ligand in the regulation of peripheral CD8+ and CD4+ T cells. Proc. Natl. Acad. Sci. USA 97: 1707-1712 [Abstract] [Full Text]
van den Brink, M. R. M., Moore, E., Horndasch, K. J., Crawford, J. M., Hoffman, J., Murphy, G. F., Burakoff, S. J. (2000). Fas-Deficient lpr Mice Are More Susceptible to Graft-Versus-Host Disease. J. Immunol. 164: 469-480 [Abstract] [Full Text]
Ashany, D., Savir, A., Bhardwaj, N., Elkon, K. B. (1999). Dendritic Cells Are Resistant to Apoptosis Through the Fas (CD95/APO-1) Pathway. J. Immunol. 163: 5303-5311 [Abstract] [Full Text]
Kreuwel, H. T. C., Morgan, D. J., Krahl, T., Ko, A., Sarvetnick, N., Sherman, L. A. (1999). Comparing the Relative Role of Perforin/Granzyme Versus Fas/Fas Ligand Cytotoxic Pathways in CD8+ T Cell-Mediated Insulin-Dependent Diabetes Mellitus. J. Immunol. 163: 4335-4341 [Abstract] [Full Text]
Ortiz, A., Lorz, C., Egido, J. (1999). The Fas ligand/Fas system in renal injury. Nephrol Dial Transplant 14: 1831-1834 [Full Text]
Thomas, H. E., Darwiche, R., Corbett, J. A., Kay, T. W. H. (1999). Evidence That {beta} Cell Death in the Nonobese Diabetic Mouse Is Fas Independent. J. Immunol. 163: 1562-1569 [Abstract] [Full Text]
Mandik-Nayak, L., Seo, S.-j., Sokol, C., Potts, K. M., Bui, A., Erikson, J. (1999). MRL-lpr/lpr Mice Exhibit a Defect in Maintaining Developmental Arrest and Follicular Exclusion of Anti-double-stranded DNA B Cells. JEM 189: 1799-1814 [Abstract] [Full Text]
Sabelko-Downes, K. A., Cross, A. H., Russell, J. H. (1999). Dual Role for Fas Ligand in the Initiation of and Recovery from Experimental Allergic Encephalomyelitis. JEM 189: 1195-1205 [Abstract] [Full Text]
Majlessi, L., Bordenave, G. (1999). Evidence of Alternative or Concomitant Use of Perforin- and Fas-Dependent Pathways in a T Cell-Mediated Negative Regulation of Ig Production. J. Immunol. 162: 4391-4398 [Abstract] [Full Text]
Cheema, Z. F., Wade, S. B., Sata, M., Walsh, K., Sohrabji, F., Miranda, R. C. (1999). Fas/Apo [Apoptosis]-1 and Associated Proteins in the Differentiating Cerebral Cortex: Induction of Caspase-Dependent Cell Death and Activation of NF-kappa B. J. Neurosci. 19: 1754-1770 [Abstract] [Full Text]
Mittelstadt, P. R., Ashwell, J. D. (1999). Role of Egr-2 in Up-regulation of Fas Ligand in Normal T Cells and Aberrant Double-negative lpr and gld T Cells. J. Biol. Chem. 274: 3222-3227 [Abstract] [Full Text]
Allison, J., Strasser, A. (1998). Mechanisms of beta �cell death in diabetes: A minor role for CD95. Proc. Natl. Acad. Sci. USA 95: 13818-13822 [Abstract] [Full Text]
Takeuchi, K., Inaba, M., Miyashima, S., Ogawa, R., Ikehara, S. (1998). A New Strategy for Treatment of Autoimmune Diseases in Chimeric Resistant MRL/lpr Mice. Blood 91: 4616-4623 [Abstract] [Full Text]
Liem, L. M., van Lopik, T., van Nieuwenhuijze, A. E.M., van Houwelingen, H. C., Aarden, L., Goulmy, E. (1998). Soluble Fas Levels in Sera of Bone Marrow Transplantation Recipients Are Increased During Acute Graft-Versus-Host Disease But Not During Infections. Blood 91: 1464-1468 [Abstract] [Full Text]
Sobel, E. S., Kakkanaiah, V. N., Schiffenbauer, J., Reap, E. A., Cohen, P. L., Eisenberg, R. A. (1998). Novel Immunoregulatory B Cell Pathways Revealed by lpr-+ Mixed Chimeras. J. Immunol. 160: 1497-1503 [Abstract] [Full Text]
Nagata, S, Golstein, P (1995). The Fas death factor. Science 267: 1449-1456 [Abstract]