Exposure of naive CD4+ T lymphocytes to superantigens such as staphylococcal enterotoxin B (SEB) induces a strong proliferative response. Prolonged exposure or subsequent restimulation of the responding T cell population with SEB leads to the apoptotic events of activation-induced cell death (AICD). However, T cells derived from either Fas-deficient lpr or Fas ligand-deficient gld autoimmune mo...

The cytoplasmic domain of Fas ligand is sufficient to costimulate CD8(+) T cells by driving Fas ligand recruitment into lipid rafts and association with select Src homology 3-containing proteins, activating PI3K and MAPK pathways, mediating nuclear translocation of the transcription factors NFAT and AP-1, and enhancing IFN-gamma production and Ag-specific CD8(+) T cell proliferation. We now sho...

Constitutively expressed Fas ligand in the cornea, Sertoli cell of the testes, Paneth cell of the intestines, and Clara cell of the airway protect surrounding parenchymal tissue by inducing apoptosis of Fas(+) immune cells during inflammatory reactions. Indeed, the action of corneal Fas ligand has been suggested to facilitate successful allogeneic cornea transplantation. To study the transcript...

Epithelium-derived Fas ligand is believed to modulate inflammation within various tissues. In this paper, we report findings that suggest a similar immunoregulatory role for Fas ligand in the lung. First, Fas ligand was localized to nonciliated, cuboidal airway epithelial cells (Clara cells) throughout the airways in the normal murine lung by employing nonisotopic in situ hybridization and immu...

Most thymocytes express high levels of Fas Ag (Apo-1/CD95); however, the role of Fas/Fas ligand-mediated apoptosis in thymocyte development remains unclear. During gestational development of thymocytes in C57BL/6(B6) +/+ mice, the highest levels of Fas ligand mRNA and Fas ligand protein expression were detected at gestational day (GD) 15, and there was a ninefold decrease in Fas ligand mRNA exp...

The aim of this study was to look at the apoptosis of alveolar lymphocytes in hypersensitivity pneumonitis (HP). HP patients and normal unexposed controls were studied. The percentage of apoptotic lymphocytes was significantly lower in HP patients than in normal patients (37.4 +/- 3.4 versus 56.5 +/- 5.5% for Annexin V and propidium iodine detection methods and 0.4 +/- 0.1 versus 1.0 +/- 0.2% f...

The membrane-bound form of Fas ligand (FasL) signals apoptosis in target cells through engagement of the death receptor Fas, whereas the proteolytically processed, soluble form of FasL does not induce cell death. However, soluble FasL can be rendered active upon cross-linking. Since the minimal extent of oligomerization of FasL that exerts cytotoxicity is unknown, we engineered hexameric protei...

Misseri, R., D. R. Meldrum, C. A. Dinarello, P. Dagher, K. L. Hile, R. C. Rink, and K. K. Meldrum. TNFmediates obstructioninduced renal tubular cell apoptosis and proapoptotic signaling. Am J Physiol Renal Physiol 288: F406–F411, 2005. First published October 26, 2004; doi:10.1152/ajprenal.00099.2004.—Obstruction of the upper urinary tract induces a progressive loss in renal mass through apopto...

Graft-versus-host disease (GVHD) and infections are two major complications of allogeneic bone marrow transplantation (BMT). In the course of GVHD, one of the pathways that activated cytotoxic T cells use to execute their killing mechanisms is the Fas/Fas ligand pathway. This killing mechanism might be accompanied by the release of soluble Fas (sFas) in the circulation. To examine the associati...