Journal article

Negative selection of seminature CD4( )8(-)HSA( ) thymocytes requires the BH3-only protein Bim but is independent of death receptor signaling

A Villunger, VS Marsden, YF Zhan, M Erlacher, AM Lew, P Bouillet, S Berzins, DI Godfrey, WR Heath, A Strasser

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2004

Abstract

T cell receptor/CD3 ligation induces apoptosis in semimature CD4(+)8(-)HSA+ thymocytes, and this helps establish immunological tolerance and constitutes one of the safeguards against autoimmune disease. We analyzed several knockout and transgenic mouse lines and found that T cell receptor/CD3-ligation-induced killing of semimature thymocytes occurred independently of Fas and "death receptor" signaling in general but required the proapoptotic BH3-only protein Bim and could be inhibited by Bcl-2. Loss of Apaf-1 or caspase-9, which act downstream of the Bcl-2 family protein family, provided only minor protection, indicating that the "apoptosome" functions as an amplifier rather than as an essen..

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