Ligation of CD8 leads to apoptosis of thymocytes that have not undergone positive selection.
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.
Grebe
Kristie M
KM
Integtrated Department of Immunology, National Jewish Medical and Research Center and University of Colorado Health Science Center, Denver, CO 80206, USA.
Clarke
Raedun L
RL
Potter
Terry A
TA
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*
D000906:Antibodies; D017252:CD3 Complex; D016827:CD8 Antigens; D003432:Cross-Linking Reagents; D015395:Histocompatibility Antigens Class I