Apoptosis of nur77/N10-transgenic thymocytes involves the Fas/Fas ligand pathway.
The orphan nuclear receptor Nur77/N10 has recently been demonstrated to be involved in apoptosis of T cell hybridomas. We report here that chronic expression of Nur77/N10 in thymocytes of transgenic mice results in a dramatic reduction of CD4+CD8+ double-positive as well as CD4+CD8- and CD4-CD8+ single-positive cell populations due to an early onset of apoptosis. CD4-CD8- double-negative and CD25+ precursor cells, however, are unaffected. Moreover, nur77/N10-transgenic thymocytes show increased expression of Fas ligand (FasL), while the levels of the Fas receptor (Fas) are not increased. The mouse spontaneous mutant gld (generalized lymphoproliferative disease) carries a point mutation in the extracellular domain of the FasL gene that abolishes the ability of FasL to bind to Fas. Thymuses from nur77/N10-transgenic mice on a gld/gld background have increased cellularity and an almost normal profile of thymocyte subpopulations. Our results demonstrate that one pathway of apoptosis triggered by Nur77/N10 in double-positive thymocytes occurs through the upregulation of FasL expression resulting in increased signaling through Fas.
Pubmed ID: 8643610 RIS Download
Animals | Antigens, CD2 | Antigens, CD95 | Apoptosis | Atrophy | Base Sequence | CD4-Positive T-Lymphocytes | CD8-Positive T-Lymphocytes | DNA Primers | DNA-Binding Proteins | Fas Ligand Protein | Flow Cytometry | Growth Hormone | Humans | Ligands | Membrane Glycoproteins | Mice | Mice, Transgenic | Molecular Sequence Data | Nuclear Receptor Subfamily 4, Group A, Member 1 | Polymerase Chain Reaction | RNA, Messenger | Receptors, Cytoplasmic and Nuclear | Receptors, Steroid | T-Lymphocytes | Thymus Gland | Transcription Factors | Transcription, Genetic