Unimpaired thymic and peripheral T cell death in mice lacking the nuclear receptor NGFI-B (Nur77).
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.
Lee
S L
SL
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Wesselschmidt
R L
RL
Linette
G P
GP
Kanagawa
O
O
Russell
J H
JH
Milbrandt
J
J
D000818:Animals; D000906:Antibodies; D017209:Apoptosis; D017252:CD3 Complex / Q000276:immunology / Q000502:physiology; D002478:Cells, Cultured; D017637:Clonal Deletion; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D018390:Gene Targeting; D006825:Hybridomas; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells; D016176:T-Lymphocyte Subsets / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D000906:Antibodies; D017252:CD3 Complex; D004268:DNA-Binding Proteins; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors