The action of Bax and bcl-2 on T cell selection.
T cell development and selection in the thymus are shaped by the induction of apoptosis. However, a direct role in T cell development and selection for any of the molecules known to regulate apoptosis has remained controversial. We have studied the effect of bax and bcl-2 transgenes in recombination activation gene 1-deficient (RAG-1(-/-)) mice transgenic for the major histocompatibility complex class I-restricted F5 T cell receptor. Overexpression of a bax transgene in the thymus seriously impairs the production of mature T cells, whereas bcl-2 overexpression greatly promotes it. The effect of bax and bcl-2 overexpression on antigen-induced negative selection was studied using fetal thymic organ cultures. This analysis showed that Bcl-2 strongly inhibits negative selection, whereas Bax does not affect it. Our data directly show that Bcl-2 family members have specific roles in T cell selection and also lend support to the hypothesis that Bax and Bcl-2 can antagonize each other's action in a certain apoptosis pathway while in another they can be functionally nonreciprocal.
Williams
O
O
Division of Molecular Immunology, Medical Research Council, National Institute for Medical Research, London, United Kingdom.
Norton
T
T
Halligey
M
M
Kioussis
D
D
Brady
H J
HJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002469:Cell Separation; D005333:Fetus; D005434:Flow Cytometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D019076:Transgenes / Q000276:immunology; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein