title: Ligation of CD8 leads to apoptosis of thymocytes that have not undergone positive selection.
abstract: Thymocytes that are not positively selected are said to undergo "death by neglect." We have found that ligation of CD8, either by antibodies or MHC class I molecules, induces apoptosis of CD4(+)CD8+ double-positive (DP) thymocytes. The susceptibility of thymocytes to CD8-mediated apoptosis is developmentally regulated and confined to a subpopulation of DP thymocytes. Stimulation through CD3 protects thymocytes from CD8-mediated apoptosis. We suggest that during thymocyte development, binding of CD8 to MHC class I molecules without T cell receptor engagement induces apoptosis in immature DP thymocytes. Our data are consistent with a model in which thymocytes that do not survive positive selection undergo "death by instruction" instead of death by neglect.
authors.affiliation: Integtrated Department of Immunology, National Jewish Medical and Research Center and University of Colorado Health Science Center, Denver, CO 80206, USA.
authors.forename: Kristie M
authors.initials: KM
authors.lastname: Grebe
authors.forename: Raedun L
authors.initials: RL
authors.lastname: Clarke
authors.forename: Terry A
authors.initials: TA
authors.lastname: Potter
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D017252:CD3 Complex / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism*; D003432:Cross-Linking Reagents; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development*
chemical_list: D000906:Antibodies; D017252:CD3 Complex; D016827:CD8 Antigens; D003432:Cross-Linking Reagents; D015395:Histocompatibility Antigens Class I