Unimpaired Thymic and Peripheral T Cell Death in Mice Lacking the Nuclear Receptor NGFI-B (Nur77)

• Published in: Science (American Association for the Advancement of Science) Vol. 269; no. 5223; pp. 532 - 535
• Main Authors: Lee, Stephen L., Wesselschmidt, Robin L., Linette, Gerald P., Kanagawa, Osami, Russell, John H., Milbrandt, Jeffrey
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 28-07-1995; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Animals; Antibodies; Antigen receptors, T cell; Apoptosis; Biological and medical sciences; CD3 Complex - immunology; CD3 Complex - physiology; Cell death; Cells, Cultured; Cellular biology; Clonal Deletion; Crosses, Genetic; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Targeting; Genetics; Hybridomas; Immunobiology; Kinetics; Lymph nodes; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Male; Mice; Mice, Transgenic; Mutation; Nuclear Receptor Subfamily 4, Group A, Member 1; Receptors; Receptors, Antigen, T-Cell, alpha-beta - physiology; Receptors, Cytoplasmic and Nuclear; Receptors, Steroid - genetics; Receptors, Steroid - physiology; RNA probes; Rodents; Stem Cells; T cell antigen receptors; T cells; T lymphocytes; T-Lymphocyte Subsets - cytology; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Thymocytes; Thymus; Thymus gland; Thymus Gland - cytology; Transcription Factors - genetics; Transcription Factors - physiology; Transgenes; Transgenic animals; Vertebrata; Mammalia; T cell receptor; Gene; Mouse; Cell death; Rodentia; T-Lymphocyte; Transgenic animal; Mutation; Immediate early gene; Apoptosis
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.7624775

T cell hybridomas require the immediate-early gene NGFI-B (nur77) for T cell receptor (TCR)-mediated apoptosis, a model for negative selection of self-reactive T cells. TCR-mediated death was examined in mice bearing an NGFI-B loss-of-function mutation, either by administration of antibodies to CD3 (anti-CD3) or in two well-characterized transgenic models expressing self-reactive TCRs. Both the extent and the rate of thymocyte death were unimpaired. Anti-CD3-induced death was normal in CD4$^+$ peripheral T cells, in which death is mediated predominantly by the Fas signaling pathway. Thus, no unique requirement for NGFI-B is observed for thymic or peripheral T cell death.